Effective drug therapy relies on the interplay between the pharmacokinetics and pharmacodynamics (PK/PD) of the agent upon administration. During the initial stages of drug discovery, numerous studies are performed to assess the pharmacological effectiveness of new chemical entities (NCEs) to select a lead compound(s) that offers the greatest promise for therapeutic efficacy. While the ability of a drug to bind to a therapeutic target is critical to its clinical success, the ultimate effectiveness is also a function of its ability to reach the therapeutic target in sufficient concentrations to mitigate or treat the ailment. Therefore, the pharmacokinetics of any NCE must also be evaluated early in the drug discovery stages to enhance the rational selection of a lead compound from the many NCEs that are screened, based on not only biological activity but also potential in vivo bioavailability. Bioavailability is defined by the US FDA as “the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action” (21 CFR 320.1(a)). The overall bioavailability is largely determined by the absorption, distribution, metabolism, and excretion (ADME) of selected compounds in targeted patient populations.While ADME involves transport/ permeability processes across cellular barriers in numerous tissues, we will restrict our discussion to intestinal absorption (absorptive influx) and excretion (secretory efflux).
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References
Acimovic, Y., and Coe, I.R. 2002. Molecular evolution of the equilibrative nucleoside transporter family: identification of novel family members in prokaryotes and eukaryotes. Mol. Biol. Evol. 19(12):2199-2210.
Adibi, S.A. 1997. The oligopeptide transporter (PepT1) in human intestine: biology and function. Gastroenterology 113:322-340.
Adibi, S.A.2003. Regulation of expression of the intestinal oligopeptide trans-porter(Pept-1) in health and disease. Am. J. Physiol. Gastrointest. Liver Physiol. 285(5):G779-G788.
Adson, A., Burton, P.S., Raub, T.J., Barsuhn, C.L., Audus, K.L., and Ho, N.F. 1995. Pas-sive diffusion of weak organic electrolytes across Caco-2 cell monolayers: uncoupling the contributions of hydrodynamic, transcellular, and paracellular barriers. J. Pharm. Sci. 84 (10):1197-1204.
Akiyama, S.I., Cornwell, M.M., Kuwano, M., Pastan, I., and Gottesman, M.M. 1988. Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog. Mol. Pharmacol. 33:144-147.
Allikmets, R., Schriml, L.M., Hutchinson, A., Romano-Spica, V., and Dean, M. 1998. A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res. 58(23):5337-5339.
Almquist, K.C., Loe, D.W., Hipfner, D.R., Mackie, J.E., Cole, S.P., and Deeley, R.G. 1995. Characterization of the 190 kDa multidrug resistance protein (MRP) in drug-selected and transfected human tumor cells. Cancer Res. 55:102-110.
Amasheh, S., Wenzel, U., Boll, M., Dom, D., Weber, W., and Clauss, W.D.H. 1997. Transport of charged dipeptides by the intestinal H+/peptide symporter PepT1 expressed in Xenopus laevis oocytes. J. Membr. Biol. 155:247-256.
Angeletti, R.H., Bergwerk, A.J., Novikoff, P.M., and Wolkoff, A.W. 1998. Dichotomous development of the organic anion transport protein in liver and choroid plexus. Am. J. Physiol. 275:C882-C887.
Arima, H., Yunomae, K., Hirayama, F., and Uekama, K. 2001. Contribution of P-glycoprotein to the enhancing effects of dimethyl-a-cyclodextrin on oral bioavailability of tacrolimus. J. Pharmacol. Exp. Ther. 297:547-555.
Ashida, K., Katsura, T., Motohashi, H., Saito, H., and Inui, K.I. 2002. Thyroid hormone regulates the activity and expression of the peptide transporter PepT1 in Caco-2 cells. Am. J. Physiol. Gastrointest. Liver Physiol. 282:G617-G623.
Ashida, K., Katsura, T., Saito, H., and Inui, K. 2004. Decreased activity and expression of intestinal oligopeptide transporter PEPT1 in rats with hyperthyroidism in vivo. Pharm. Res. 21(6):969-975.
Bailey, D.G., Malcolm, J., Arnold, O., and Spence, J.D. 1998. Grapefruit juice-drug interactions. Br. J. Clin. Pharmacol. 46:101-110.
Bailey, P.D., Boyd, C.A., Bronk, J.R., Collier, I.D., Meredith, D., Morgan, K.M., and Temple, C.S. 1999. How to make drugs orally active: a substrate model for the pep-tide transporter PepT1. Angew Chem. Int. Ed. Engl. 39:505-508.
Bakos, E., Hegedus, T., Hollo, Z., Welker, E., Tusnady, G.E., Zaman, G.J., Flens, M.J., Varadi, A., and Sarkadi, B. 1996. Membrane topology and glycosylation of the human multidrug resistance-associated protein. J. Biol. Chem. 271(21):12322-12326.
Baldwin, S.A., Beal, P.R., Yao, S.Y.M., King, A.E., Cass, C.E., and Young, J.D. 2004. The equilibrative nucleoside transporter family, SLC29. Plugers Arch. Eur. J. Physiol. 447:735-743.
Baldwin, S.A., Yao, S.Y., Hyde, R.J., Ng, A.M., Foppolo, S., Barnes, K., Ritzel, M.W., Cass, C.E., and Young, J.D. 2005. Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J. Biol. Chem. 280(16):15880-15887.
Balimane, P.V., and Sinko, P.J. 2000. Effect of ionization on the variable uptake of valacyclovir via the human intestinal peptide transporter (hPepT1) in CHO cells. Biopharm. Drug Dispos. 21:165-174.
Barendt, W.M., and Wright, S.H. 2002. The human organic cation transporter (hOCT2) recognizes the degree of substrate ionization. Biol. Chem. 277:22491-22496.
Bates, S.E., Mickley, L.A., Chen, Y.N., Richert, N., Rudick, J., Biedler, J.L., and Fojo, A.T. 1989. Expression of a drug resistance gene in human neuroblastoma cellines: modula-tion by retinoic acid-induced differentiation. Mol. Cell. Biol. 9:4337-4344.
Belinsky, M.G., Bain, L.J., Balsara, B.B., Testa, J.R., and Kruh, G.D. 1998. J. Natl Cancer. Inst. 90:1735-1741.
Belinsky, M.G., Chen, Z.S., Shchaveleva, I., Zeng, H., and Kruh, G.D. 2002. Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 62(21):6172-6177.
Benet, L.Z., and Cummins, C.L. 2001. The drug efflux-metabolism alliance: biochemical aspects. Adv. Drug Deliv. Rev. 50(Suppl. 1): S3-S11.
Bera, T.K., Lee, S., Salvatore, G., Lee, B., and Pastan, I. 2001. MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer. Mol. Med. 7(8):509-516.
Bera, T.K., Iavarone, C., Kumar, V., Lee, S., Lee, B., and Pastan, I. 2002. MRP9, an unusual truncated member of the ABC transporter superfamily, is highly expressed in breast cancer. Proc. Natl. Acad. Sci. USA 99(10):6997-7002.
Berlioz, F., Julien, S., Tsocas, A., Chariot, J., Carbon, C., Farinotti, R., and Roze, C. 1999. Neural modulation of cephalexin intestinal absorption through the di- and tripeptide brush border transporter of rat jejunum in vivo. J. Pharmacol. Exp. Ther. 288:1037-1044.
Berlioz, F., Maoret, J.J., Paris, H., Laburthe, M., Farinotti, R., and Roze, C. 2000. Alpha(2)-adrenergic receptors stimulate oligopeptide transport in a human intestinal cell line. J. Pharmacol. Exp. Ther. 294:466-472.
Bhardwaj, R.K., Glaeser, H., Becquemont, L., Klotz, U., Gupta, S.K., and Fromm, M.F. 2002. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J. Pharmacol. Exp. Ther. 302:645-650.
Bhardwaj, R.K., Herrera-Ruiz, D., Eltoukhy, N., Saad, M., and Knipp, G.T. (2005a). The functional evaluation of human peptide/histidine transporter1(hPHT1) in transiently transfected COS-7cells. Eur. J. Pharm. Sci.(Epub ahead of print; DOI:10.1016/j.ejps.2005.09.014).
Bhardwaj, R.K., Herrera-Ruiz, D., Sinko, P.J., Gudmundsson, O.S., and Knipp, G. 2005b. Delineation of HPEPT1 meditated uptake and transport of substrates with varying trans-porter affinities utilizing stably transfected HPEPT1/MDCK clones and Caco-2 cells. J. Pharmacol. Exp. Ther. 314(3):1093-1100.
Biegel, A., Gebauer, S., Hartrodt, B., Brandsch, M., Neubert, K., and Thondorf, I. 2005. Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J. Med. Chem. 48(13):4410-4419.
Bolger, M.B., Haworth, I.S., Yeung, A.K., Ann, D., von Grafenstein, H., Hamm-Alvarez, S., Okamoto, C.T., Kim, K.J., Basu, S.K., Wu, S., and Lee, V.H. 1998. Structure, function, and molecular modeling approaches to the study of the intestinal dipeptides transporter PepT1. J. Pharm. Sci. 87:1286-1291.
Botka, C.W., Witting, T.W., Graul, R.C., Nielsen, C.U., Sad ée, W., Higaki, K., and Amidon, G.L. 2000. Human proton/oligopeptide transporter (POT) genes: identifica-tion of putative human genes using bioinformatics. AAPS Pharm Sci 2:Article 16.
Brandsch, M., Miyamoto, Y., Ganapathy, V., and Leibach, F.H. 1994. Expression and protein kinase C-dependent regulation of peptide/H+ co-transport system in the Caco-2 human colon carcinoma cell line. Biochem. J. 299:253-260.
Brandsch, M., Knutter, I., and Leibach, F.H. 2004. The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur. J. Pharm. Sci. 21(1):53-60.
Burt, R.K., and Thorgeirsson, S.S. 1988. Coinduction of MDR-1 multidrug resistance and cytochrome P-450 genes in rat liver by xenobiotics. J. Natl Cancer Inst. 80:1383-1386.
Busch, A.E., Quester, S., Ulzheimer, J.C., Waldegger, S., Gorboulev, V., Arndt, P., Lang, F., and Koepsell, H. 1996. Electrogenic properties and substrate specificity of the polyspe-cific rat cation transporter rOCT1. J. Biol. Chem. 271:32599-32604.
Busch, A.E., Karbach, U., Miska, D., Gorboulev, V., Akhoundova, A., Volk, C., Arndt, P., Ulzheimer, J.C., Sonders, M.S., Baumann, C., Waldegger, S., Lang, F., and Koepsell, H. 1998. Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol. Pharma-col. 54:342-352.
Buyse, M., Berlioz, F., Guilmeau, S., Tsocas, A., Voisin, T., P éranzi, G., Merlin, D., Laburthe, M., Lewin, M.J.M., Rozé, C., and Bado, A. 2001. PepT1-mediated epithe-lial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine. J. Clin. Invest. 108:1483-1494.
Carpenter, L., and Halestrap, A.P. 1994. The kinetics, substrate and inhibitor specificity of the lactate transporter of Ehrlich-Lettre tumour cells studied with the intracellular pH indicator BCECF. Biochem. J. 304:751-760.
Chang, C., Swaan, P.W., Ngo, L.Y., Lum, P.Y., Patil, S.D., and Unadkat, J.D. 2004. Molecular requirements of the human nucleoside transporters hCNT1, hCNT2, and hENT1. Mol. Pharmacol. 65(3):558-570.
Chaudhary, P.M., and Roninson, I.B. 1991. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell 66(1):85-94.
Chaudhary, P.M., and Roninson, I.B. 1993. Induction of multidrug resistance in human cells by transient exposure to different chemotherapeutic drugs. J. Natl Cancer. Inst. 85 (8):632-639.
Chen, H., Wong, E.A., and Webb, K.E. 1999. Tissue distribution of a peptide transporter mRNA in sheep, dairy cows, pigs, and chickens. J. Anim. Sci. 77:1277-1283.
Chen, X.-Z., Steel, A., and Hediger, M.A. 2000. Functional roles of histidine and tyro-sine residues in the H+-peptide transporter PepT1. Biochem. Biophys. Res. Commun. 272:726-730.
Chen, Z.S., Lee, K., and Kruh, G.D.2001. Transport of cyclic nucleotides and estradiol17-beta-D-glucuronide by multidrug resistance protein4. Resistance to 6-mercaptopurine and 6-thioguanine. J. Biol. Chem. 276(36):33747-33754.
Chen, Z.S., Lee, K., Walther, S., Raftogianis, R.B., Kuwano, M., Zeng, H., and Kruh, G.D. 2002. Analysis of methotrexate and folate transport by multidrug resistance protein 4(ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer. Res. 62(11):3144-3150.
Chen, Z.S., Hopper-Borge, E., Belinsky, M.G., Shchaveleva, I., Kotova, E., and Kruh, G.D. 2003. Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol. Pharmacol. 63(2):351-358.
Chen, Z.S., Guo, Y., Belinsky, M.G., Kotova, E., and Kruh, G.D. 2005. Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol. Pharmacol. 67(2):545-557.
Cheng, X., Maher, J., Chen, C., and Klaassen, C.D. 2005. Tissue distribution and ontogeny of mouse organic anion transporting polypeptides (Oatps). Drug Metab. Dis-pos. 33:1062-1073.
Cherrington, N.J., Hartley, D.P., Li, N., Johnson, D.R., and Klaassen, C.D. 2002. Organ distribution of multidrug resistance proteins 1, 2, and 3 (Mrp1, 2, and 3) mRNA and hepatic induction of Mrp3 by constitutive androstane receptor activators in rats. J. Pharmacol. Exp. Ther. 300(1):97-104.
Chin, K.V., Tanaka, S., Darlington, G., Pastan, I., and Gottesman, M.M. 1990. Heat shock and arsenite increase expression of the multidrug resistance (MDR1) gene in human renal carcinoma cells. J. Biol. Chem. 265:221-226.
Chiou, W.L., Chung, S.M., and Wu, T.C. 2000. Apparent lack of effect of P-glycoprotein on the gastrointestinal absorption of a substrate, tacrolimus, in normal mice. Pharm. Res. 17:205-208.
Choudhuri, S., Ogura, K., and Klaassen, C.D. 2001. Cloning, expression, and ontogeny of mouse organic anion-transporting polypeptide-5, a kidney-specific organic anion transporter. Biochem. Biophys. Res. Commun. 280:92-98.
Ciarimboli, G., and Schlatter, E. 2005. Regulation of organic cation transport. Pflugers Arch. 449:423-441.
Clark, H.F., Gurney, A.L., Abaya, E., Baker, K., Baldwin, D., Brush, J., Chen, J., Chow, B., Chui, C., Crowley, C., Currell, B., Deuel, B., Dowd, P., Eaton, D., Foster, J., Grimaldi, C., Gu, Q., Hass, P.E., Heldens, S., Huang, A., Kim, H.S., Klimowski, L., Jin, Y., Johnson, S., Lee, J., Lewis, L., Liao, D., Mark, M., Robbie, E., Sanchez, C., Schoenfeld, J., Seshagiri, S., Simmons, L., Singh, J., Smith, V., Stinson, J., Vagts, A., Vandlen, R., Watanabe, C., Wieand, D., Woods, K., Xie, M.-H., Yansura, D., Yi, S., Yu, G., Yuan, J., Zhang, M., Zhang, Z., Goddard, A., Wood, W.I., and Godowski, P. 2003. The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 13(10):2265-2270.
Cole, S.P., Bhardwaj, G., Gerlach, J.H., Mackie, J.E., Grant, C.E., Almquist, K.C., Stewart, A.J., Kurz, E.U., Duncan, A.M., and Deeley, R.G. 1992. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258 (5088):1650-1654.
Cole, S.P., Sparks, K.E., Fraser, K., Loe, D.W., Grant, C.E., Wilson, G.M., and Deeley, R.G. 1994. Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res. 54(22):5902-5910.
Coe, I.R., Griffiths, M., Young, J.D., Baldwin, S.A., and Cass, C.E. 1997. Assignment of the human equilibrative nucleoside transporter (hENT1) to 6p21.1-p21.2. Genomics 45 (2):459-460.
Coe, I., Zhang, Y., McKenzie, T., and Naydenova, Z. 2002. PKC regulation of the human equilibrative nucleoside transporter, hENT1. FEBS Lett. 517:201-205.
Cornwell, M.M., Safa, A.R., Felsted, R.L., Gottesman, M.M., and Pastan, I. 1986. Mem-brane vesicles from multidrug-resistant human cancer cells contain a specific 150-to 170-kDa protein detected by photoaffinity labeling. Proc. Natl Acad. Sci. USA 83:3847-3850.
Courtois, A., Payen, L., Guillouzo, A., and Fardel, O. 1999. Up-regulation of multidrug resistance-associated protein 2 (MRP2) expression in rat hepatocytes by dexamethasone. FEBS Lett. 459(3):381-385.
Covitz, Y.K.-M., Amidon, G.L., and Sad ée, W. 1998. Membrane topology of the human dipeptides transporter, hPepT1, determined by epitope insertions. Biochemistry 37:15214-15221.
Crawford, C.R., Patel, D.H., Naeve, C., and Belt, J.A. 1998. Cloning of the human equi-librative, nitrobenzylmercaptopurine riboside (NBMPR)-insensitive nucleoside trans-porter ei by functional expression in a transport-deficient cell line. J. Biol. Chem. 273:5288-5293.
Cronstein, B.N. 1994. Adenosine, an endogenous anti-inflammatory agent. J. Appl. Physiol. 76:5-13.
Cuff, M.A., Lambert, D.W., and Shirazi-Beechey, S.P. 2002. Substrate-induced regulation of the human colonic monocarboxylate transporter, MCT1. J. Physiol. 539:361-371.
Cuff, M., Dyer, J., Jones, M., and Shirazi-Beechey, S. 2005. The human colonic monocarboxylate transporter isoform 1: its potential importance to colonic tissue homeostasis. Gastroenterology 128:676-686.
Damaraju, V.L., Visser, F., Zhang, J., Mowles, D., Ng, A.M., Young, J.D., Jayaram, H.N., and Cass, C.E. 2005. Role of human nucleoside transporters in the cellular uptake of two inhibitors of IMP dehydrogenase, tiazofurin and benzamide riboside. Mol. Pharma-col. 67(1):273-279.
Daniel, H. 1996. Function and molecular structure of brush border membrane peptide/H+ symporters. J. Memb. Biol. 154:197-203.
Dantzig, A.H., Hoskins, J.A., Tabas, L.B., Bright, S., Shepard, R.L., Jenkins, I.L., Duckworth, D.C., Sportsman, J.R., Mackensen, D., Rosteck, P.R., Jr., and Skatrud, P.L. 1994. Association of intestinal peptide transport with a protein related to the cadherin superfamily. Science 264:430-433.
Dautrey, S., Felice, K., Petiet, A., Lacour, B., Carbon, C., and Farinotti, R. 1999. Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates. Br. J. Pharmacol. 127:1728-1734.
Del Santo, B., Valdes, R., Mata, J., Felipe, A., Casado, F.J., and Pastor-Anglada, M. 1998. Differential expression and regulation of nucleoside transport systems in rat liver parenchymal and hepatoma cells. Hepatology 28:1504-1511.
Dietrich, C.G., de Waart, D.R., Ottenhoff, R., Schoots, I.G., and Elferink, R.P. 2001. Increased bioavailability of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in MRP2-deficient rats. Mol. Pharmacol. 59(5):974-980.
D öring, F., Dorn, D., Bachfisher, U., Amasheh, S., Herget, M., and Daniel, H. 1996. Func-tional analysis of a chimeric mammalian peptide transporter derived from the intestinal and renal isoforms. J. Physiol. 497:773-779.
D öring, F., Martini, C., Walter, J., and Daniel, H. 2002. Importance of a small N-terminal region in mammalian peptide transporters for substrate affinity and function. J. Membr. Biol. 186:55-62.
Doyle, L.A., Yang, W., Abruzzo, L.V., Krogmann, T., Gao, Y., Rishi, A.K., and Ross, D.D. 1998. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc. Natl Acad. Sci. USA 95:15665-15670.
Drenou, B., Fardel, O., Amiot, L., and Fauchet, R. 1993. Detection of P glycoprotein activity on normal and leukemic CD34+ cells. Leuk Res. 17(12):1031-1035.
Dresser, G.K., Bailey, D.G., Leake, B.F., Schwarz, U.I., Dawson, P.A., Freeman, D.J., and Kim, R.B. 2002. Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine. Clin. Pharmacol. Ther. 71:11-20.
Duflot, S., Calvo, M., Casado, F.J., Enrich, C., and Pastor-Anglada, M. 2002. Concentrative nucleoside transporter (rCNT1) is targeted to the apical membrane through the hepatic transcytotic pathway. Exp. Cell Res. 281(1):77-85.
Dumitrescu, A.M., Liao, X.H., Best, T.B., Brockmann, K., and Refetoff, S. 2004. A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am. J. Hum. Genet. 74:168-175.
Dunwiddie, T.V. 1985. The physiological role of adenosine in the central nervous system. Int. Rev. Neurobiol. 27:63-139.
D ürr, D., Stieger, B., Kullak-Ublick, G.A., Rentsch, K.M., Steinert, H.C., Meier, P.J., and Fattinger, K. 2000. St John’s Wort induces intestinal P-glycoprotein/MDR1 and intesti-nal and hepatic CYP3A4. Clin. Pharmacol. Ther. 68:598-604.
Dussault, I., Lin, M., Hollister, K., Wang, E.H., Synold, T.W., and Forman, B.M. 2001. Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. J. Biol. Chem. 276(36):33309-33312.
Ekins, S., Waller, C.L., Swaan, P.W., Cruciani, G., Wrighton, S.A., and Wikel, J.H. 2000. Progress in predicting human ADME parameters in silico. J. Pharmacol. Toxicol. Methods 44(1):251-272.
Ekins, S., Nikolsky, Y., and Nikolskaya, T. 2005. Techniques: application of systems biology to absorption, distribution, metabolism, excretion and toxicity. Trends Pharmacol. Sci. 26(4):202-209.
Engel, K., Zhou, M., and Wang, J. 2004. Identification and characterization of a novel monoamine transporter in the human brain. J. Biol. Chem. 279(48):50042-50049.
Ely, S.W., and Berne, R.M. 1992. Protective effects of adenosine in myocardial ischemia. Circulation 85:893-904.
Emoto, A., Ushigome, F., Koyabu, N., Kajiya, H., Okabe, K., Satoh, S., Tsukimori, K., Nakano, H., Ohtani, H., and Sawada, Y. (2002). H(+)-linked transport of salicylic acid, an NSAID, in the human trophoblast cell line BeWo. Am. J. Physiol. 282:C1064-C1075.
Enerson, B.E., and Drewes, L.R. (2003). Molecular features, regulation and function of monocarboxylate transporters: implications for drug delivery. J. Pharm. Sci. 92:1531-1544.
Fain, J.N., and Malbon, C.C. 1979. Regulation of adenylate cyclase by adenosine. Mol. Cell. Biochem. 25:143-169.
Fei, Y.J., Kanai, Y., Nussberger, S., Ganapathy, V., Leibach, F.H., Romero, M.F., Singh, S.K., Boron, W.F., and Hediger, M.A. 1994. Expression cloning of a mammalian proton-coupled oligopeptide transporter. Nature 368:563-566.
Fei, Y.J., Liu, W., Prasad, P.D., Kekuda, R., Oblak, T.G., Ganapathy, V., and Leibach, F.H. 1997. Identification of the histidyl residue obligatory for the catalytic activity of the human H+/peptide cotransporters PepT1 and PepT2. Biochemistry 14:452-460.
Fei, Y.J., Ganapathy, V., and Leibach, F.H. 1998. Molecular and structural features of the proton-coupled oligopeptide transporter superfamily. Prog. Nucleic. Acid. Res. Mol. Biol. 58:239-261.
Fei, Y.J., Sugawara, M., Liu, J.C., Li, H.W., Ganapathy, V., Ganapathy, M.E., and Leibach, F.H. 2000. cDNA structure, genomic organization, and promoter analy-sis of the mouse intestinal peptide transporter PepT1. Biochim. Biophys. Acta 1492: 145-154.
Ferry, D.R., Russell, M.A., and Cullen, M.H. 1992. P-glycoprotein possesses a 1,4-dihydropyridine-selective drug acceptor site which is allosterically coupled to a vincaalkaloid-selective binding site. Biochem. Biophys. Res. Commun. 188:440-445.
Ferte, J. 2002. Analysis of tangled relationships between P-glycoprotein mediated mul-tidrug resistance and the lipid phase of the cell membrane. Eur. J. Biochem. 267:277-294 .
Fisher, G.A., Lum, B.L., Hausdorff, J., and Sikic, B.I. 1996. Pharmacological considera-tions in the modulation of multidrug resistance. Eur. J. Cancer 32A(6):1082-1088.
Flens, M.J., Zaman, G.J., Van Der Valk, P., Izquierdo, M.A., Schroeijers, A.B., Scheffer, G.L., Van Der Groep, P., De Haas, M., Meijer, C.J., and Scheper, R.J. 1996. Tissue distribution of the multidrug resistance protein. Am. J. Pathol. 148:1237-1247.
Fletcher, C., and Bean, B. 1985. Evaluation of oral aciclovir therapy. Drug Intell. Clin. Pharm. 19:518-524.
Fojo, A.T., Ueda, K., Slamon, D.J., Poplack, D.G., Gottesman, M.M., and Pastan, I. 1987. Expression of a multidrug-resistance gene in human tumors and tissues. Proc. Natl Acad. Sci. USA 84(1):265-269.
Friedrich, A., Prasad, P.D., Freyer, D., Ganapathy, V., and Brust, P. 2003. Molecular cloning and functional characterization of the OCTN2 transporter at the RBE4 cells, an in vitro model of the blood-brain barrier. Brain Res. 968:69-79.
Friedrichsen, G.M., Chen, W., Begtrup, M., Lee, C.P., Smith, P.L., and Borchardt, R.T. 2002. Synthesis of analogs of L-valacyclovir and determination of their substrate activ-ity for the oligopeptide transporter in Caco-2 cells. Eur. J. Pharm. Sci. 16(1-2):1-13.
Friesema, E.C., Grueters, A., Biebermann, H., Krude, H., von Moers, A., Reeser, M., Barrett, T.G., Mancilla, E.E., Svensson, J., Kester, M.H., Kuiper, G.G., Balkassmi, S., Uitterlinden, A.G., Koehrle, J., Rodien, P., Halestrap, A.P., and Visser, T.J. 2004. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet 364:1435-1437.
Friesema, E.C., Jansen, J., Milici, C., and Visser, T.J. 2005. Thyroid hormone transporters. Vitam. Horm. 70:137-167.
Fromm, M.F., Kauffman, H.M., Fritz, P., Burk, O., Kroemer, H.K., Warzok, R.W., Eichelbaum, M., Siegmund, W., and Schrenk, D. 2000. The effect of rifampin treatment on intestinal expression of human MRP transporters. Am. J. Pathol. 157:1575-1580.
Ganapathy, M.E., Huang, W., Rajan, D.P., Carter, A.L., Sugawara, M., Iseki, K., Leibach, F.H., and Ganapathy, V. 2000. Beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J. Biol. Chem. 275:1699-1707.
Gangopadhyay, A., Thamotharan, M., and Adibi, S.A. 2002. Regulation of oligopeptide transporter (Pept-1) in experimental diabetes. Am. J. Physiol. Gastrointest. Liver Physiol. 283 (1):G133-G138.
Garcia, C.K., Goldstein, J.L., Pathak, R.K., Anderson, R.G., and Brown, M.S. 1994. Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell 76:865-873.
Gatmaitan, Z.C., and Arias, I.M. 1993. Structure and function of P-glycoprotein in normal liver and small intestine. Adv. Pharmacol. 24:77-97.
Gebauer, S., Knutter, I., Hartrodt, B., Brandsch, M., Neubert, K., and Thondorf, I. 2003. Three-dimensional quantitative structure-activity relationship analyses of pep-tide substrates of the mammalian H+/peptide cotransporter PEPT1. J. Med. Chem. 46 (26):5725-5734 .
Germann, U.A., Pastan, I., and Gottesman, M.M. 1993. P-glycoproteins: mediators of multidrug resistance. Semin. Cell. Biol. 4(1):63-76.
Gill, R.K., Saksena, S., Alrefai, W.A., Sarwar, Z., Goldstein, J.L., Carroll, R.E., Ramaswamy, K., and Dudeja, P.K. 2005. Expression and membrane localization of MCT isoforms along the length of the human intestine. Am. J. Physiol. Cell Physiol. 289 (4):C846-C852.
Glavy, J.S., Wu, S.M., Wang, P.J., Orr, G.A., and Wolkoff, A.W. 2000. Down-regulation by extracellular ATP of rat hepatocyte organic anion transport is mediated by serine phosphorylation of Oatp1. J. Biol. Chem. 275:1479-1484.
Gomez-Angelats, M., Del Santo, B., Mercader, J., Ferrer-Martinez, A., Felipe, A., Casado, J., and Pastor-Anglada, M. 1996. Hormonal regulation of concentrative nucle-oside transport in liver parenchymal cells. Biochem. J. 313:915-920.
Gorboulev, V., Ulzheimer, J.C., Akhoundova, A., Ulzheimer-Teuber, I., Karbach, U., Quester, S., Baumann, C., Lang, F., Busch, A.E., and Koepsell, H. 1997. Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 16:871-881.
Gotoh, Y., Kato, Y., Stieger, B., Meier, P.J., and Sugiyama, Y. 2002. Gender difference in the Oatp1-mediated tubular reabsorption of estradiol 17beta-D-glucuronide in rats. Am. J. Physiol. Endocrinol. Metab. 282:E1245-E1254.
Gottesman, M.M., and Pastan, I. 1993. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem. 62:385-427.
Graul, R.C., and Sad ée, W. 1997. Sequence alignments of the H(+)-dependent oligopep-tide transporter family PTR: Inferences on structure and function of the intestinal PEPT1 transporter. Pharm. Res. 14:388-400.
Gray, J.H., Owen, R.P., and Giacomini, K.M. 2004. The concentrative nucleoside transporter family, SLC28. Pflugers Arch. Eur. J. Physiol. 447:728-734.
Greiner, B., Eichelbaum, M., Fritz, P., Kreichgauer, H.P., von Richter, O., Zundler, J., and Kroemer, H.K. 1999. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J. Clin. Invest. 104(2):147-153.
Griffiths, D.A., and Jarvis, S.M. 1996. Nucleoside and nucleobase transport systems of mammalian cells. Biochim. Biophys. Acta 1286:153-181.
Griffiths, M., Beaumont, N., Yao, S.Y.M., Sundaram, M., Boumah, C.E., Davies, A., Kwong, F.Y.P., Coe, I.R., Cass, C.E., Young, J.D., Baldwin, S.A. 1997a. Cloning of a human nucleoside transporter implicated in the cellular uptake of adenosine and chemotherapeutic drugs. Nat. Med. 3(1):89-93.
Griffiths, M., Yao, S.Y., Abidi, F., Phillips, S.E., Cass, C.E., Young, J.D., and Baldwin, S.A. 1997b. Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta. Biochem. J. 328 (3):739-743.
Grundemann, D., Gorboulev, V., Gambaryan, S., Veyhl, M., and Koepsell, H. 1994. Drug excretion mediated by a new prototype of polyspecific transporter. Nature 372:549-552.
Guo, G.L., and Klaassen, C.D. 2001. Protein kinase C suppresses rat organic anion trans-porting polypeptide 1- and 2-mediated uptake. J. Pharmacol. Exp. Ther. 299:551-557
Guo, G.L., Johnson, D.R., and Klaassen, C.D. 2002a. Postnatal expression and induction by pregnenolone-16α-carbonitrile of the organic anion-transporting polypeptide 2 in rat liver. Drug Metab. Dispos. 30:283-288.
Guo, G.L., Staudinger, J., Ogura, K., and Klaassen, C.D. 2002b. Induction of rat organic anion transporting polypeptide 2 by pregnenolone-16alpha-carbonitrile is via interaction with pregnane X receptor. Mol. Pharmacol. 61:832-839.
Guo, Y., Kotova, E., Chen, Z.S., Lee, K., Hopper-Borge, E., Belinsky, M.G., and Kruh, G.D. 2003. MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2-3-dideoxycytidine and 9-(2-phosphonylmethoxyethyl)-adenine. J. Biol. Chem. 278:29509-29514.
Gutmann, H., Hruz, P., Zimmermann, C., Beglinger, C., and Drewe, J. 2005. Distribution of breast cancer resistance protein (BCRP/ABCG2) mRNA expression along the human GI tract. Biochem. Pharmacol. 70(5):695-699.
Hagenbuch, B., and Meier, P.J. 2003. The superfamily of organic anion transporting polypeptides. Biochim. Biophys. Acta 1609:1-18.
Hagenbuch, B., and Meier, P.J. 2004. Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers. Arch. 447:653-665.
Hahn, E.L., Halestrap, A.P., and Gamelli, R.L. 2000. Expression of the lactate transporter MCT1 in macrophages. Shock 13:253-260.
Halestrap, A.P., and Meredith, D. 2004. The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch. Eur. J. Physiol. 447:619-628.
Halestrap, A.P., and Price, N.T. 1999. The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem. J. 343(Pt 2):281-299.
Hamilton, S.R., Yao, S.Y., Ingram, J.C., Hadden, D.A., Ritzel, M.W., Gallagher, M.P., Henderson, P.J., Cass, C.E., Young, J.D., and Baldwin, S.A. 2001. Subcellular distribution and membrane topology of the mammalian concentrative Na+-nucleoside cotransporter rCNT1. J. Biol. Chem. 276(30):27981-27988.
Hamman, M.A., Bruce, M.A., Haehner-Daniels, B.D., and Hall, S.D. 2001. The effect of rifampin administration on the disposition of fexofenadine. Clin. Pharmacol. Ther. 69 (3):114-121.
Harrison, A.P., Erlwanger, K.H., Elbrond, V.S., Andersen, N.K., and Unmack, M.A. 2004. Gastrointestinal-tract models and techniques for use in safety pharmacology. J. Pharmacol. Toxicol. Methods 49(3):187-199.
Hayer-Zillgen, M., Bruss, M., and Bonisch, H. 2002. Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br. J. Pharmacol. 136:829-836.
Hediger, M.A., Romero, M.F., Peng, J.B., Rolfs, A., Takanaga, H., and Bruford, E.A. 2004. The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins Introduction. Pflugers Arch. 447 (5):465-468.
Herrera-Ruiz, D., and Knipp, G.T. 2003. Current Perspectives on Established and Putative Mammalian Oligopeptide Transporters. J. Pharm. Sci. 92(4):691-714.
Herrera-Ruiz, D., Wang, Q., Gudmundsson, O.S., Cook, T.J., Smith, R.L., Faria, T.N., and Knipp, G.T. 2001. Spatial expression patterns of peptide transporters in the human and rat gastrointestinal tracts, Caco-2 in vitro cell culture, and multiple human tissues. AAPS Pharm Sci 3(1):Article 9 (DOI: 10.1208/ps030109).
Higgins, C.F. 1991. Molecular basis of multidrug resistance mediated by P-glycoprotein. Curr. Opin. Biotechnol. 2(2):278-281.
Higgins, C.F., and Gottesman, M.M. 1992. Is the multidrug transporter a flippase? Trends Biochem. Sci. 17(1):18-21.
Higuchi, T., and Davis, S.S. 1970. Thermodynamic analysis of structure-activity relation-ships of drugs. Prediction of optimal structure. J. Pharm. Sci. 59(10):1376-1383.
Hipfner, D.R., Almquist, K.C., Leslie, E.M., Gerlach, J.H., Grant, C.E., Deeley, R.G., and Cole, S.P. 1997. Membrane topology of the multidrug resistance protein (MRP), A study of glycosylation-site mutants reveals an extracytosolic NH2 terminus. J. Biol. Chem. 272(38):23623-23630.
Hirohashi, T., Suzuki, H., and Sugiyama, Y. 1999. Characterization of the transport properties of cloned rat multidrug resistance-associated protein 3 (MRP3). J. Biol. Chem. 274:15181-15185.
Hirohashi, T., Suzuki, H., Takikawa, H., and Sugiyama, Y. 2000. ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (Mrp3). J. Biol. Chem. 275:2905-2910.
Hoffmeyer, S., Burk, O., von Richter, O., Arnold, H.P., Brockmoller, J., Johne, A., Cascorbi, I., Gerloff, T., Roots, I., Eichelbaum, M., and Brinkmann, U. 2000. Func-tional polymorphisms of the human multidrug-resistance gene: multiple sequence vari-ations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc. Natl Acad. Sci. USA 97(7):3473-3478.
Hogben, C.A.M., Tocco, D.J., Brodie, B.B., and Schanker, L.S. 1959. On the mechanism of intestinal absorption of drugs. J. Pharmacol. Exp. Ther. 125:275-282.
Honda, Y., Ushigome, F., Koyabu, N., Morimoto, S., Shoyama, Y., Uchiumi, T., Kuwano, M., Ohtani, H., and Sawada, Y. 2004. Effects of grapefruit juice and orange juice components on P-glycoprotein and MRP2 mediated drug efflux. Br. J. Pharmacol. 143 (7):856-864.
Hooijberg, J.H., Broxterman, H.J., Kool, M., Assaraf, Y.G., Peters, G.J., Noordhuis, P., Scheper, R.J., Borst, P., Pinedo, H.M., and Jansen, G. 1999. Antifolate resistance medi-ated by the multidrug resistance proteins MRP1 and MRP2. Cancer. Res. 59:2532-2535.
Hopper, E., Belinsky, M.G., Zeng, H., Tosolini, A., Testa, J.R., and Kruh, G.D. 2001. Analysis of the structure and expression pattern of MRP7 (ABCC10), a new member of the MRP subfamily. Cancer Lett. 162:181-191.
Hopper-Borge, E., Chen, Z.S., Shchaveleva, I., Belinsky, M.G., and Kruh, G.D. 2004. Analysis of the drug resistance profile of multidrug resistance protein 7 (ABCC10): resistance to docetaxel. Cancer Res. 64(14):4927-4930.
Hosoya, K., Kondo, T., Tomi, M., Takanaga, H., Ohtsuki, S., and Tersaki, T. 2001. MCT1-mediated transport of L-lactic acid at the inner blood-retinal barrier: a possible route for delivery of monocarboxylic acid drugs to the retina. Pharm. Res. 18:1669-1676.
Huang, Q.Q., Yao, S.Y., Ritzel, M.W., Paterson, A.R., Cass, C.E., and Young, J.D. 1994. Cloning and functional expression of a complementary DNA encoding a mammalian nucleoside transport protein. J. Biol. Chem. 269:17757-17760.
Hugger, E.D., Novak, B.L., Burton, P.S., Audus, K.L., and Borchardt, R.T. 2002. A com-parison of commonly used polyethoxylated pharmaceutical excipients on their ability to inhibit P-glycoprotein activity in vitro. J. Pharm. Sci. 91:1991-2002.
Hussain, I., Kellett, G.L., Affleck, J., Shepherd, E.J., and Boyd, C.A.R. 2002. Expression and cellular distribution during development of the peptide transporter (PepT1) in the small intestinal epithelium of the rat. Cell. Tissue Res. 307:139-142.
Hyafil, F.C., Vergely, P., and Vigneaud, T. 1993. Grand-Perret: in vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Res. 53:4595-4602.
Hyde, R.J., Cass, C.E., Young, J.D., and Baldwin, S.A. 2001. The ENT family of eukary-ote nucleoside and nucleobase transporter: recent advances in the investigation of struc-ture/function relationships and the identification of novel isoforms. Mol. Membr. Biol. 18 (1):53-63.
Ieiri, I., Takane, H., and Otsubo, K. 2004. The MDR1 (ABCB1) gene polymorphism and its clinical implications. Clin. Pharmacokinet. 43(9):553-576.
Ihara, T., Tsujikawa, T., Fujiyama, Y., and Bamba, T. 2000. Regulation of PepT1 peptide transporter expression in the rat small intestine under malnourished conditions. Digestion 61:59-67.
Imai, Y., Asada, S., Tsukahara, S., Ishikawa, E., Tsuruo, T., and Sugimoto, Y. 2003. Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol. Pharmacol. 64:610-618.
Inokuchi, A., Hinoshita, E., Iwamoto, Y., Kohno, K., Kuwano, M., and Uchiumi, T. 2001. Enhanced expression of the human multidrug resistance protein 3 by bile salt in human enterocytes. A transcriptional control of a plausible bile acid transporter. J. Biol. Chem. 276 (50):46822-46829.
Irie, M., Terada, T., Sawada, K., Saito, H., and Inui, K.-I. 2001. Recognition and transport characteristics of nonpeptidic compounds by basolateral peptide transporter in Caco-2 cells. J. Pharmacol. Exp. Ther. 298:711-717.
Irie, M., Terada, T., Okuda, M., and Inui, K.-I. 2004. Efflux properties of basolateral peptide transporter in human intestinal cell line Caco-2. Pflugers Arch. 449(2):186-194.
Irie, M., Terada, T., Katsura, T., Matsuoka, S., and Inui, K.I. 2005. Computational mod-elling of H+-coupled peptide transport via human PEPT1. J. Physiol. 565(Pt 2):429-439.
Ishikawa, T., Tsuji, A., Inui, K., Sai, Y., Anzai, N., Wada, M., Endou, H., and Sumino, Y. 2004. The genetic polymorphism of drug transporters: functional analysis approaches. Pharmacogenomics 5(1):67-99.
Itoh, T., Tanno, M., Li, Y.-H., and Yamada, H. 1998. Transport of phenethicillin into rat intestinal brush border membrane vesicles: role of the monocarboxylic acid transport system. Int. J. Pharm. 172:103-112.
Izzo, A.A. 2005. Herb-drug interactions: an overview of the clinical evidence. Fundam. Clin. Pharmacol. 19(1):1-16.
Jacobs, M.H. 1940. Some aspects of cell permeability to weak electrolytes. Cold Spring Harbor Symp. Quant. Biol. 8:30-39.
Jancis, E.M., Carbone, R., Loechner, K.J., and Dannies, P.S. 1993. Estradiol induction of rhodamine 123 efflux and the multidrug resistance pump in rat pituitary cells. Mol. Pharmacol. 43:51-56.
Jedlitschky, G., Leier, I., Buchholz, U., Barnouin, K., Kurz, G., and Keppler, D. 1996. Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Res. 56:988-994.
Jedlitschky, G., Leier, I., Buchholz, U., Hummel-Eisenbeiss, J., Burchell, B., and Keppler, D. 1997. ATP-dependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2. Biochem. J. 327 (Pt 1):305-310.
Jennings, L.L., Hao, C., Cabrita, M.A., Vickers, M.F., Baldwin, S.A., Young, J.D., and Cass, C.E. 2001. Distinct regional distribution of human equilibrative nucleoside trans-porter proteins 1 and 2 (hENT1 and hENT2) in the central nervous system. Neurophar-macology 40:722-731.
Jimenez, A., Pubill, D., Pallas, M., Camins, A., Llado, S., Camarasa, J., and Escubedo, E. 2000. Further characterization of an adenosine transport system in the mitochondrial fraction of rat testis. Eur. J. Pharmacol. 298:31-39.
Joly, B., Fardel, O., Cecchelli, R., Chesne, C., Puzzo, C., and Guillouzo, A. 1995. Selective drug transport and P-glycoprotein activity in an in-vitro blood brain barrier model. Tox. In Vitro 9:357-364.
Jonker, J.W., and Schinkel, A.H. 2004. Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3). J. Pharmacol. Exp. Ther. 308(1):2-9.
Jonker, J.W., Smit, J.W., Brinkhuis, R.F., Maliepaard, M., Beijnen, J.H., Schellens, J.H., and Schinkel, A.H. 2000. Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J. Natl Cancer. Inst. 92(20):1651-1656.
Jonker, J.W., Wagenaar, E., Mol, C.A., Buitelaar, M., Koepsell, H., Smit, J.W., and Schinkel, A.H. 2001. Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Oct1 [Slc22a1]) gene. Mol. Cell Biol. 21:5471-5477.
Juliano, R.T., and Ling, V.A. 1976. Surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta 455:152-162.
Jung, D., Hagenbuch, B., Gresh, L., Pontoglio, M., Meier, P.J., and Kullak-Ublick, G.A. 2001. Characterization of the human OATP-C (SLC21A6) gene promoter and regula-tion of liver-specific OATP genes by hepatocyte nuclear factor 1 alpha. J. Biol. Chem. 276:37206-37214.
Jung, D., Podvinec, M., Meyer, U.A., Mangelsdorf, D.J., Fried, M., Meier, P.J., and Kullak-Ublick, G.A. 2002. Human organic anion transporting polypeptide 8 pro-moter is transactivated by the farnesoid X receptor/bile acid receptor. Gastroenterology 122:1954-1966.
Karlsson, J., Kuo, S.M., Ziemniak, J., and Artursson, P. 1993. Transport of celiprolol across human intestinal epithelial (Caco-2) cells: mediation of secretion by multiple transporters including P-glycoprotein. Br. J. Pharmacol. 110:1009-1016.
Kassel, D.B. 2004. Applications of high-throughput ADME in drug discovery. Curr. Opin. Chem. Biol. 8(3):339-345.
Kast, H.R., Goodwin, B., Tarr, P.T., Jones, S.A., Anisfeld, A.M., Stoltz, C.M., Tontonoz, P., Kliewer, S., Willson, T.M., and Edwards, P.A. 2002. Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor and constitutive androstane receptor. J. Biol. Chem. 277:2908-2915.
Katsura, T., and Inui, K. 2003. Intestinal absorption of drugs mediated by drug trans-porters: mechanisms and regulation. Drug Metab. Pharmacokinet. 18:1-15.
Kauffman, D.W., Kelly, J.P., Rosenberg, L., Anderson, T.E., and Mitchell, A.A. 2002. Recent patterns of medication use in the ambulatory adult population of the United States. JAMA 287:337-344.
Kauffmann, H.M., Keppler, D., Gant, T.W., and Schrenk, D. 1998. Induction of hepatic mrp2 (cmrp/cmoat) gene expression in nonhuman primates treated with rifampicin or tamoxifen. Arch. Toxicol. 72(12):763-768.
Kawasaki, Y., Kato, Y., Sai, Y., and Tsuji, A. 2004. Functional characterization of human organic cation transporter OCTN1 single nucleotide polymorphisms in the Japanese population. J. Pharm. Sci. 93:2920-2926.
Kekuda, R., Prasad, P.D., Wu, X., Wang, H., Fei, Y.J., Leibach, F.H., and Ganapathy, V. 1998. Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J. Biol. Chem. 273:15971-15979.
Keppler, D., Leier, I., and Jedlitschky, G. 1997. Transport of glutathione conjugates and glucuronides by the multidrug resistance proteins MRP1 and MRP2. Biol. Chem. 378 (8):787-791.
Kerb, R., Brinkmann, U., Chatskaia, N., Gorbunov, D., Gorboulev, V., Mornhinweg, E., Keil, A., Eichelbaum, M., and Koepsell, H. 2002. Identification of genetic variations of the human organic cation transporter hOCT1 and their functional consequences. Phar-macogenetics 12:591-595.
Kim, R.B. 2003. Organic anion-transporting polypeptide (OATP) transporter family and drug disposition. Eur. J. Clin. Invest. 33(Suppl 2):1-5.
Kim, C.M., Goldstein, J.L., and Brown, M.S. 1992. cDNA cloning of MEV, a mutant pro-tein that facilitates cellular uptake of mevalonate, and identification of the point mutation responsible for its gain of function. J. Biol. Chem. 267:23113-23121.
Kim, R.B., Fromm, M.F., Wandel, C., Leake, B., Wood, A.J., Roden, D.M., and Wilkinson, G.R. 1998. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J. Clin. Invest. 101(2):289-294.
Kim, D.K., Kanai, Y., Chairoungdua, A., Matsuo, H., Cha, S.H., and Endou, H. 2001a. Expression cloning of a Na+-independent aromatic amino acid transporter with struc-tural similarity to H+/monocarboxylate transporters. J. Biol. Chem. 276:17221-17228.
Kim, D.K., Kanai, Y., Matsuo, H., Kim, J.Y., Chairoungdua, A., Kobayashi, Y., Enomoto, A., Cha, S.H., Goya, T., and Endou, H. 2001b. The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location. Genomics 79:95-103.
Kim, S.J., Masaki, T., Leypoldt, J.K., Kamerath, C.D., Mohammad, S.F., and Cheung, A.K. 2004. Arterial and venous smooth-muscle cells differ in their responses to antiproliferative drugs. J. Lab. Clin. Med. 144(3):156-162.
Kimberlin, D.F., Weller, S., Whitley, R.J., Andrews, W.W., Hauth, J.C., Lakeman, F., and Miller, G. 1998. Pharmacokinetics of oral valacyclovir and acyclovir in late pregnancy. Am. J. Obstet. Gynecol. 179(4):846-851.
Kimura, T., and Higaki, K. 2002. Gastrointestinal transit and drug absorption. Biol. Pharm. Bull. 25(2):149-164.
Kimura, H., Takeda, M., Narikawa, S., Enomoto, A., Ichida, K., and Endou, H. 2002. Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J. Pharmacol. Exp. Ther. 301:293-298.
Kirk, P., Wilson, M.C., Heddle, C., Brown, M.H., Barclay, A.N., and Halestrap, A.P. 2000. CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO J. 19:3896-3904.
Kiss, A., Farah, K., Kim, J., Garriock, R.J., Drysdale, T.A., and Hammond, J.R. 2000. Molecular cloning and functional characterization of inhibitor-sensitive (mENT1) and inhibitor-resistant (mENT2) equilibrative nucleoside transporters from mouse brain. Biochem. J. 352(2):363-372.
Klaassen, C.D. 1972. Immaturity of the newborn rat’s hepatic excretory function for ouabain. J. Pharmacol. Exp. Ther. 183:520-526.
Klang, J.E., Burnworth, L.A., Pan, Y.X., Webb, K.E. Jr., and Wong, E.A. 2005. Functional characterization of a cloned pig intestinal peptide transporter (pPepT1). J. Anim. Sci. 83 (1):172-181.
Knipp, G.T., and Herrera-Ruiz, D. (2004). Filing date: 5/31/01, Issued: 1/27/04. US Patent no. 6,683,169: “Nucleic acid encoding the human peptide histidine transporter 1 and methods of use thereof.”
Knipp, G.T., Ho, N.F., Barsuhn, C.L., and Borchardt, R.T. 1997. Paracellular diffusion in Caco-2 cell monolayers: effect of perturbation on the transport of hydrophilic compounds that vary in charge and size. J. Pharm. Sci. 86(10):1105-1110.
Kobayashi, D., Nozawa, T., Imai, K., Nezu, J., Tsuji, A., and Tamai, I. 2003. Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane. Pharmacol. Exp. Ther. 306:703-708.
Koepsell, H. 2004. Polyspecific organic cation transporters: their functions and interactions with drugs. Trends. Pharmacol. Sci. 25:375-381.
Koepsell, H., and Endou, H. 2004. The SLC22 drug transporter family. Pflugers. Arch. 447:666-676.
Koepsell, H., Schmitt, B.M., and Gorboulev, V. 2003. Organic cation transporters. Rev. Physiol. Biochem. Pharmacol. 150:36-90.
Kong, W., Engel, K., and Wang, J. 2004. Mammalian Nucleoside Transporters. Curr. Drug Metab. 5:63-84.
Konig, J., Nies, A.T., Cui, Y., Leier, I., and Keppler, D. 1999. Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance. Biochim. Biophys. Acta 1461:377-394.
Konig, J., Cui, Y., Nies, A.T., and Keppler, D. 2000a. A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane. Am. J. Physiol. Gastrointest. Liver Physiol. 278:G156-G164.
Konig, J., Cui, Y., Nies, A.T., and Keppler, D. 2000b. Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide. J. Biol. Chem. 275:23161-23168.
Kool, M., De Haas, M., Scheffer, G.L., Scheper, R.J., Van Eijk, M.J., Juijn, J.A., Baas, F., and Borst, P. 1997. Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer. Res. 57:3537-3547.
Kottra, G., Stamfort, A., and Daniel, H. 2002. PEPT1 as a paradigm for membrane carriers that mediate electrogenic bidirectional transport of anionic, cationic and neutral substrates. J. Biol. Chem. 277(36):32683-32691.
Kovarik, J.M., Rigaudy, L., Guerret, M., Gerbeau, C., and Rost, K.L. 1999. Longitudinal assessment of a P-glycoprotein-mediated drug interaction of valspodar on digoxin. Clin. Pharmacol. Ther. 66(4):391-400.
Kramer, R., Weber, T.K., and Arceci, R. 1995. Inhibition of N-linked glycosylation of P-glycoproptein by tunicamycin results in a reduced multidrug resistance phenotype. Br. J. Cancer. 71:670-676.
Krishna, R., and Mayer, L.D. 2000. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci. 11(4):265-83.
Kruh, G.D., and Belinsky, M.G. 2003. The MRP family of drug efflux pumps. Oncogene 22:7537-7352.
Kubota, T., Furukawa, T., Tanino, H., Suto, A., Otan, Y., Watanabe, M., Ikeda, T., and Kitajima, M. 2001. Resistant mechanisms of anthracyclines-pirarubicin might partly break through the P-glycoprotein-mediated drug-resistance of human breast cancer tis-sues. Breast Cancer 8(4):333-338.
Kulkarni, A.A., Haworth, I.S., and Lee, V.H. 2003a. Transmembrane segment 5 of the dipeptide transporter hPepT1 forms a part of the substrate translocation pathway. Biochem. Biophys. Res. Commun. 306(1):177-185.
Kulkarni, A.A., Haworth, I.S., Uchiyama, T., and Lee, V.H. 2003b. Analysis of transmem-brane segment 7 of the dipeptide transporter hPepT1 by cysteine-scanning mutagenesis. J. Biol. Chem. 278(51):51833-51840.
Kunta, J.R., and Sinko, P.J. 2004. Intestinal drug transporters: in vivo function and clinical importance. Curr. Drug Metab. 5:109-124.
Kurata, Y., Ieiri, I., Kimura, M., Morita, T., Irie, S., Urae, A., Ohdo, S., Ohtani, H., Sawada, Y., Higuchi, S., and Otsubo, K. 2002. Role of human MDR1 gene polymor-phism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Clin. Pharmacol. Ther. 72(2):209–219.
Kusuhara, H., and Sugiyama, Y. (2002). Role of transporters in the tissue-selective distribution and elimination of drugs: transporters in the liver, small intestine, brain and kidney. J. Control Release 78(1-3):43-54.
Lahjouji, K., Mitchell, G.A., and Qureshi, I.A. 2001. Carnitine transport by organic cation transporters and systemic carnitine deficiency. Mol. Genet. Metab. 73:287-297.
Lai, L., and Tan, T.M. 2002. Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. Biochem. J. 361(Pt 3):497-503.
Lai, Y., Bakken, A.H., and Unadkat, J.D. 2002. Simultaneous expression of hCNT1-CFP and hENT1-YFP in Madin-Darby canine kidney cells. Localization and vectorial transport studies. J. Biol. Chem. 277:37711-37717.
Lai, Y., Lee, E.W., Ton, C.C., Vijay, S., Zhang, H., and Unadkat, J.D. 2005. Conserved residues F316 and G476 in the concentrative nucleoside transporter 1 (hCNT1) affect guanosine sensitivity and membrane expression, respectively. Am. J. Physiol. - Cell Physiol. 288(1):C39-C45.
Lambert, D.W., Wood, I.S., Ellis, A., and Shirazi-Beechey, S.P. 2002. Molecular changes in the expression of human colonic nutrient transporters during the transition from nor-mality to malignancy. Br. J. Cancer 86:1262-1269.
Landowski, C., Sun, D., Foster, D., Menon, S.S., Barnett, J.L., Welage, L.S., Ramachandran, C., and Amidon, G.L. 2003. Gene expression in the human intestine and correlation with oral valaciclovir pharmacokinetic parameters. J. Pharmacol. Exp. Ther. 306:778-786.
Landowski, C.P., Vig, B.S., Song, X., and Amidon, G.L. 2005. Targeted delivery to PEPT1-overexpressing cells: acidic, basic, and secondary floxuridine amino acid ester prodrugs. Mol. Cancer Ther. 4(4):659-667.
Lazar, A., Grundemann, D., Berkels, R., Taubert, D., Zimmermann, T., and Schomig, E. 2003. Genetic variability of the extraneuronal monoamine transporter EMT (SLC22A3). J. Hum. Genet. 48:226-230.
Leabman, M.K., Huang, C.C., Kawamoto, M., Johns, S.J., Stryke, D., Ferrin, D.E., De Young, J., Taylor, T., Clark, A.G., Herskowitz, I., and Giacomini, K.M. 2002 Polymorphisms in a human kidney xenobiotic transporter, OCT2, exhibit altered function. Pharmacogenetics. 12(5):395-405.
Lee, V.H.L. 2000. Membrane transporters. Eur. J. Pharm. Sci. 11:S41-S50.
Leibach, F.H., and Ganapathy, V. 1996. Peptide transport in the intestine and the kidney. Annu. Rev. Nutr. 16:99-119.
Leier, I., Jedlitschky, G., Buchholz, U., Cole, S.P., Deeley, R.G., and Keppler, D. 1994. The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and struc-turally related conjugates. J. Biol. Chem. 269:27807-27810.
Leier, I., Hummel-Eisenbeiss, J., Cui, Y., and Keppler, D. 2000. ATP-dependent paraaminohippurate transport by apical multidrug resistance protein MRP2. Kidney Int. 57 (4):1636-1642.
Leino, R.L., Gerhart, D.Z., Duelli, R., Enerson, B.E., and Drewes, L.R. 2001. Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain. Neurochem. Int. 38(6):519-527.
Leo, A., Hansch, C., and Elkins, D. 1971. Partition coefficients and their uses. Chem. Rev. 71(6):525-616.
Leslie, E.M., Ito, K., Upadhyaya, P., Hecht, S.S., Deeley, R.G., and Cole, S.P. 2001. Transport of the beta-O-glucuronide conjugate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by the multidrug resistance pro-tein 1 (MRP1). Requirement for glutathione or a non-sulfur-containing analog. J. Biol. Chem. 276(30):27846-27854.
Leslie, E.M., Deeley, R.G., and Cole, S.P. 2003. Bioflavonoid stimulation of glutathione transport by the 190-kDa multidrug resistance protein 1 (MRP1). Drug Metab. Dispos. 31:11-15.
Leslie, E.M., Deeley, R.G., and Cole, S.P. 2005. Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol. Appl. Pharmacol. 204(3):216-237.
Leung, G.P., Man, R.Y., and Tse, C.M. (2005a). d-Glucose upregulates adenosine transport in cultured human aortic smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 288:H2756-H2762.
Leung, G.P., Man, R.Y., and Tse, C.M. 2005b. Effect of thiazolidinediones on equilibra-tive nucleoside transporter-1 in human aortic smooth muscle cells. Biochem. Pharmacol. 70 (3):355-362.
Leveille-Webster, C.R., and Arias, I.M. 1995. The biology of the P-glycoproteins. J. Membr. Biol. 143(2):89-102.
Li, L., Lee, T.K., Meier, P.J., and Ballatori, N. 1998. Identification of glutathione as a driving force and leukotriene C4 as a substrate for oatp1, the hepatic sinusoidal organic solute transporter. J. Biol. Chem. 273:16184-16191.
Li, Y.H., Ito, K., Tsuda, Y., Kohda, R., Yamada, H., and Itoh, T. 1999. Mechanism of intestinal absorption of an orally active beta-lactam prodrug: uptake and transport of carindacillin in Caco-2 cells. J. Pharmacol. Exp. Ther. 290:958-964.
Li, L., Meier, P.J., and Ballatori, N. 2000. Oatp2 mediates bidirectional organic solute transport: a role for intracellular glutathione. Mol. Pharmacol. 58:335-340.
Li, N., Hartley, D.P., Cherrington, N.J., and Klaassen, C.D. 2002. Tissue expression, ontogeny, and inducibility of rat organic anion transporting polypeptide 4. J. Pharma-col. Exp. Ther. 301:551-560.
Liang, R., Fei, Y.J., Prasad, P.D., Ramamoorthy, S., Han, H., Yang-Feng, T.L., Hediger, M.A., Ganapathy, V., and Leibach, F.H. 1995. Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization. J. Biol. Chem. 270:6456-6463.
Lin, R.Y., Vera, J.C., Chaganti, R.S., and Golde, D.W. 1998. Human monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter. J. Biol. Chem. 273: 28959-28965.
Lincke, C.R., Smit, J.J., van der Velde-Koerts, T., and Borst, P. 1991. Structure of the human MDR3 gene and physical mapping of the human MDR locus. J. Biol. Chem. 266 (8):5303-5310.
Lipinski, C.A. 2000. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods 44(1):235-249.
Lipinski, C.A., Lombardo, F., Dominy, B.W., and Feeney, P.J. 1997. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 23:3-25.
Lipinski, C.A., Lombardo, F., Dominy, B.W., and Feeney, P.J. 2001. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46(1-3):3-26.
Loe, D.W., Deeley, R.G., and Cole, S.P. 2000a. Verapamil stimulates glutathione transport by the 190-kDa multidrug resistance protein 1 (MRP1). J. Pharmacol. Exp. Ther. 293:530-538.
Loe, D.W., Oleschuk, C.J., Deeley, R.G., and Cole, S.P. 2000b. Structure-activity stud-ies of verapamil analogs that modulate transport of leukotriene C(4) and reduced glutathione by multidrug resistance protein MRP1. Biochem. Biophys. Res. Commun. 275 (3):795-803.
Loewen, S.K., Ng, A.M., Yao, S.Y., Cass, C.E., Baldwin, S.A., and Young, J.D. 1999. Identification of amino acid residues responsible for the pyrimidine and purine nucle-oside specificities of human concentrative Na+nucleoside cotransporters hCNT1 and hCNT2. J. Biol. Chem. 274:24475-24484.
Lu, R., Kanai, N., Bao, Y., Wolkoff, A.W., and Schuster, V.L. 1996. Regulation of renal oatp mRNA expression by testosterone. Am. J. Physiol. 270:F332-F337.
Luo, G., Guenthner, T., Gan, L.S., and Humphreys, W.G. 2004. CYP3A4 induction by xenobiotics: biochemistry, experimental methods and impact on drug discovery and development. Curr. Drug Metab. 5:483-505.
MacDougall, C., and Guglielmo, B.J. 2004. Pharmacokinetics of valaciclovir. J. Antimicrob. Chemother. 53(6):899-901.
Mackenzie, B., Loo, D.D., Fei, Y., Liu, W.J., Ganapathy, V., Leibach, F.H., and Wright, E.M. 1996. Mechanisms of the human intestinal H+-coupled oligopeptide transporter hPEPT1. J. Biol. Chem. 271(10):5430-5437.
Mackey, J.R., Mani, R.S., Selner, M., Mowles, D., Young, J.D., Belt, J.A., Crawford, C.R., and Cass, C.E. 1998. Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines. Cancer Res. 58(19):4349-4357.
Mackey, J.R., Yao, S.Y., Smith, K.M., Karpinski, E., Baldwin, S.A., Cass, C.E., and Young, J.D. 1999. Gemcitabine transport in Xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J. Natl Cancer Inst. 91 (21):1876-1881.
Madon, J., Eckhardt, U., Gerloff, T., Stieger, B., and Meier, P.J. 1997. Functional expression of the rat liver canalicular isoform of the multidrug resistance-associated protein. FEBS Lett. 406:75-78.
Maher, J.M., Cheng, X., Slitt, A.L., Dieter, M.Z., and Klaassen, C.D. 2005. Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver. Drug Metab. Dispos. 33(7):956-962.
Maliepaard, M., van Gastelen, M.A., de Jong, L.A., Pluim, D., van Waardenburg, R.C., Ruevekamp-Helmers, M.C., Floot, B.G., and Schellens, J.H. 1999. Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res. 59 (18):4559-4563.
Maliepaard, M., Scheffer, G.L., Faneyte, I.F., van Gastelen, M.A., Pijnenborg, A.C., Schinkel, A.H., van De Vijver, M.J., Scheper, R.J., and Schellens, J.H. 2001. Subcel-lular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res. 61(8):3458-3464.
Mangravite, L.M., Lipschutz, J.H., Mostov, K.E., and Giacomini, K.M. 2001. Localization of GFP-tagged concentrative nucleoside transporters in a renal polarized epithelial cell line. Am. J. Physiol. Renal Physiol. 280(5):F879-F885.
Mangravite, L.M., Xiao, G., and Giacomini, K.M. 2003. Localization of human equilibra-tive nucleoside transporters, hENT1 and hENT2, in renal epithelial cells. Am. J. Physiol. Renal. Physiol. 284:F902-F910.
Mani, R.S., Hammond, J.R., Marjan, J.M., Graham, K.A., Young, J.D., Baldwin, S.A., and Cass, C.E. 1998. Demonstration of equilibrative nucleoside transporters (hENT1 and hENT2) in nuclear envelopes of cultured human choriocarcinoma (BeWo) cells by functional reconstitution in proteoliposomes. J. Biol. Chem. 273:30818-30825.
Martin, C., Berridge, G., Higgins, C.F., and Callaghan, R. 1997. The multi-drug resistance reversal agent SR33557 and modulation of vinca alkaloid binding to P-glycoprotein by an allosteric interaction. Br. J. Pharmacol. 122:765-771.
Masaki, T., Kamerath, C.D., Kim, S.J., Leypoldt, J.K., Mohammad, S.F., and Cheung, A.K. 2004. In vitro pharmacological inhibition of human vascular smooth muscle cell pro-liferation for the prevention of hemodialysis vascular access stenosis. Blood Purif. 22 (3):307-312.
McAleer, M.A., Breen, M.A., White, N.L., and Matthews, N. (1999). pABC11 (also known as MOAT-C and MRP5), a member of the ABC family of proteins, has anion transporter activity but does not confer multidrug resistance when overexpressed in human embryonic kidney 293 cells. J. Biol. Chem. 274:23541-23548.
Mehrens, T., Lelleck, S., Cetinkaya, I., Knollmann, M., Hohage, H., Gorboulev, V., Boknik, P., Koepsell, H., and Schlatter, E. 2000. The affinity of the organic cation trans-porter rOCT1 is increased by protein kinase C-dependent phosphorylation. J. Am. Soc. Nephrol. 11:1216-1224.
Meier, P.J., and Stieger, B. 2002. Bile salt transporters. Annu. Rev. Physiol. 64:635-661.
Meredith, D. 2004. Site-directed mutation of arginine 282 to glutamate uncouples the movement of peptides and protons by the rabbit proton-peptide cotransporter PepT1. J. Biol. Chem. 279(16):15795-15798.
Meredith, D., and Boyd, C.A.R. 2000. Structure and function of eukaryotic peptide transporters. Cell Mol. Life Sci. 57:754-778.
Merlin, D., Steel, A., Gewirtz, A.T., Si-Tahar, M., Hediger, M.A., and Madara, J.L. (1998). hPepT1-mediated epithelial transport of bacteria-derived chemotactic peptides enhances neutrophil-epithelial interactions. J. Clin. Invest. 102:2011-2018.
Merlin, D., Si-Tahar, M., Sitaraman, S.V., Eastburn, K., Williams, I., Liu, X., Hediger, M.A., and Madara, J.L. 2001. Colonic epithelial hPepT1 expression occurs in inflammatory bowel disease: transport of bacterial peptides influences expression of MHC class 1 molecules. Gastroenterology 120:1666-1679.
Mickley, A.L., Bates, S.S., Richert, N.D., Currier, S., Tanaka, S., Foss, F., Rosen, N., and Fojo, A.T. 1989. Modulation of the expression of a multidrug resistance gene (mdr-1/P-glycoprotein) by differentiating agents. J. Biol. Chem. 264:18031-18040.
Mikkaichi, T., Suzuki, T., Tanemoto, M., Ito, S., and Abe, T. 2004. The organic anion transporter (OATP) family. Drug Metab. Pharmacokinet. 19(3):171-179.
Mizuno, N., Niwa, T., Yotsumoto, Y., and Sugiyama, Y. 2003. Impact of drug transporter studies on drug discovery and development. Pharmacol. Rev. 55:425-461.
van Montfoort, J.E., Hagenbuch, B., Groothuis, G.M., Koepsell, H., Meier, P.J., and Meijer, D.K. 2003. Drug uptake systems in liver and kidney. Curr. Drug Metab. 4:185-211.
Moriya, Y., Nakamura, T., Horinouchi, M., Sakaeda, T., Tamura, T., Aoyama, N., Shirakawa, T., Gotoh, A., Fujimoto, S., Matsuo, M., Kasuga, M., and Okumura, K. 2002. Effects of polymorphisms of MDR1, MRP1, and MRP2 genes on their mRNA expression levels in duodenal enterocytes of healthy Japanese subjects. Biol. Pharm. Bull. 25(10):1356-1359.
Mouly, S., and Paine, M.F. 2003. P-glycoprotein increases from proximal to distal regions of human small intestine. Pharm. Res. 20(10):1595-1599.
Muller, U., Brandsch, M., Prasad, P.D., Fei, Y.-J., Ganapathy, V., and Leibach, F.H. 1996. Inhibition of the H+/peptide cotransporter in the human intestinal cell line Caco-2 by cyclic AMP. Biochem. Biophys. Res. Commun. 218:461-465.
Nagel, G., Volk, C., Friedrich, T., Ulzheimer, J.C., Bamberg, E., and Koepsell, H. (1997). A reevaluation of substrate specificity of the rat cation transporter rOCT1. J. Biol. Chem. 272:31953-31956.
Nakatomi, I., Yoshikawa, M., Oka, M., Ikegami, Y., Hayasaka, S., Sano, K., Shiozawa, K., Kawabata, S., Soda, H., Ishikawa, T., Tanabe, S., and Kohno, S. 2001. Transport of 7-ethyl-10-hydroxycamptothecin (SN-38) by breast cancer resistance protein ABCG2 in human lung cancer cells. Biochem. Biophys. Res. Commun. 288:827-832.
Naruhashi, K., Tamai, I., Inoue, N., Muraoka, H., Sai, Y., Suzuki, N., and Tsuji, A. 2002. Involvement of multidrug resistance-associated protein 2 in intestinal secretion of grepafloxacin in rats. Antimicrob. Agents Chemother. 46:344-349.
Nerurkar, M.M., Burton, P.S., and Borchardt, R.T. 1996. The use of surfactants to enhance the permeability of peptides through Caco-2 cells by inhibition of an apically polarized efflux system. Pharm. Res. 13:528-534.
Nerurkar, M.M., Ho, N.F., Burton, P.S., Vidmar, T.J., and Borchardt, R.T. 1997. Mechanistic roles of neutral surfactants on concurrent polarized and passive membrane transport of a model peptide in Caco-2 cells. J. Pharm. Sci. 86:813-821.
Nezu, J., Tamai, I., Oku, A., Ohashi, R., Yabuuchi, H., Hashimoto, N., Nikaido, H., Sai, Y., Koizumi, A., Shoji, Y., Takada, G., Matsuishi, T., Yoshino, M., Kato, H., Ohura, T., Tsu-jimoto, G., Hayakawa, J., Shimane, M., and Tsuji, A. 1999. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat. Genet. 21:91-94.
Ngo, L.Y., Patil, S.D., and Unadkat, J.D. 2001. Ontogenic and longitudinal activity of Na+-nucleoside transporters in the small intestine. Am. J. Physiol. 280:G475-G481.
Nielsen, C.U., Brodin, B., Jorgensen, F., Frokjaer, S., and Steffansen, B. 2002. Human peptide transporters: therapeutic applications. Expert Opin. 12:1329-1350.
Nies, A.T., Cantz, T., Brom, M., Leier, I., and Keppler, D. 1998. Expression of the apical conjugate export pump, Mrp2, in the polarized hepatoma cell line, WIF-B. Hepatology 28 (5):1332-1340.
Nozawa, T., Nakajima, M., Tamai, I., Noda, K., Nezu, J., Sai, Y., Tsuji, A., and Yokoi, T. 2002. Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis. Pharmacol. Exp. Ther. 302:804-813.
Nozawa, T., Toyobuku, H., Kobayashi, D., Kuruma, K., Tsuji, A., and Tamai, I. 2003. Enhanced intestinal absorption of drugs by activation of peptide transporter PEPT1 using proton-releasing polymer. J. Pharm. Sci. 92(11):2208-2216.
Nozawa, T., Imai, K., Nezu, J., Tsuji, A., and Tamai, I. 2004. Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J. Pharmacol. Exp. Ther. 308:438-445.
Nussberger, S., Steel, A., and Hediger, M. 1997a. Structure and pharmacology of protonlinked peptide transporters. J. Control Rel. 46:31-38.
Nussberger, S., Steel, A., Trott, D., Romero, M., Boron, W.F., and Hediger, M. 1997b. Symmetry of H+ binding to the intra- and extracellular side of the H+-coupled oligopeptide cotransporter PepT1. J. Biol. Chem. 272:7777-7785.
Ogihara, H., Suzuki, T., Nagamachi, Y., Inui, K.-I., and Takata, K. 1999. Peptide transporter in the rat small intestine: ultrastructural localization and the effect of starvation and administration of amino acids. Histochem. J. 31:169-174.
Oh, D.-M., and Amidon, G.L. 1999. Overview of membrane transport. In Membrane Transporters as Drug Targets. Edited by , Kluwer Acad-emic/Plenum Publishers, New York, NY, pp. 1-27.
Ohashi, R., Tamai, I., Yabuuchi, H., Nezu, J.I., Oku, A., Sai, Y., Shimane, M., and Tsuji, A. 1999. Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J. Pharmacol. Exp. Ther. 291:778-784.
Okamura, A., Emoto, A., Koyabu, N., Ohtani, H., and Sawada, Y. 2002. Transport and uptake of nateglinide in Caco-2 cells and its inhibitory effect on human monocarboxylate transporter MCT1. Br. J. Pharmacol. 137:391-399.
Okuda, M., Saito, H., Urakami, Y., Takano, M., and Inui, K. (1996). cDNA cloning and functional expression of a novel rat kidney organic cation transporter, OCT2. Biochem. Biophys. Res. Commun. 224:500-507.
Okuda, M., Urakami, Y., Saito, H., and Inui, K.I. 1999. Molecular mechanisms of organic cation transport in OCT2-expressing Xenopus oocytes. Biochim. Biophys. Acta 1417:224-231.
Owen, M.R., Doran, E., and Halestrap, A.P. 2000. Evidence that metformin exerts its antidiabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J. 348:607-614.
Ozvegy, C., Litman, T., Szakacs, G., Nagy, Z., Bates, S., Varadi, A., and Sarkadi, B. 2001. Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem. Biophys. Res. Commun. 285(1):111-117.
Pan, Y.X., Wong, E.A., Bloomquist, J.R., and Webb, K.E., Jr. 2001. Expression of a cloned ovine gastrointestinal peptide transporter (oPepT1) in Xenopus oocytes induces uptake of oligopeptides in vitro. J. Nutr. 131:1264-1270.
Pastor-Anglada, M., Casado, F.J., Valdes, R., Mata, J., Garcia-Manteiga, J., and Molina, M. 2001. Complex regulation of nucleoside transporter expression in epithelial and immune system cells. Mol. Memb. Bio. 18:81-85.
Paulusma, C.C., Bosma, P.J., Zaman, G.J., Bakker, C.T., Otter, M., Scheffer, G.L., Scheper, R.J., Borst, P., and Oude Elferink, R.P. 1996. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science 271:1126-1128.
Pavlova, A., Sakurai, H., Leclercq, B., Beier, D.R., Yu, A.S., and Nigam, S.K. 2000. Developmentally regulated expression of organic ion transporters NKT (OAT1), OCT1, NLT (OAT2), and Roct. Am. J. Physiol. Renal Physiol. 278:F635-F643.
Pawelczyk, T., Podgorska, M., and Sakowicz, M. 2003. The effect of insulin on expression level of nucleoside transporters in diabetic rats. Mol. Pharmacol. 63(1):81-88.
Peltekova, V.D., Wintle, R.F., Rubin, L.A., Amos, C.I., Huang, Q., Gu, X., Newman, B., Van Oene, M., Cescon, D., Greenberg, G., Griffiths, A.M., St George-Hyslop, P.H., and Siminovitch, K.A. 2004. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat. Genet. 36:471-475.
Peng, K.C., Cluzeaud, F., Bens, M., Van Huyen, J.P., Wioland, M.A., Lacave, R., and Vandewalle, A. 1999. Tissue and cell distribution of the multidrug resistance-associated protein (MRP) in mouse intestine and kidney. J. Histochem. Cytochem. 47:757-768.
Pennycooke, M., Chaudary, N., Shuralyova, I., Zhang, Y., and Coe, I.R. 2001. Differential expression of human nucleoside transporters in normal and tumor tissue. Biochem. Biophys. Res. Commun. 280:951-959.
Phan, D., Chin-Hong, P., Lin, E., Anderle, P., Sadee, W., and Guglielmo, B.J. 2003. Intraand interindividual variabilities of valaciclovir oral bioavailability and effect of coadministration of an hPEPT1 inhibitor. Antimicrob. Agents Chemother. 47:2351-2353.
Phillis, J.W., and Wu, P.H. 1981. The role of adenosine and its nucleotides in central synaptic transmission. Prog. Neurobiol. 16:187-239.
Philp, N.J., Yoon, H., and Grollman, E.F. 1998. Monocaroxylate transporter (MCT1) is located in the apical membrane and MCT3 in the basal membrane of rat RPE. Am. J. Physiol. 274:R1824-R1828.
Philp, N.J., Ochrietor, J.D., Rudoy, C., Muramatsu, T., and Linser, P.J. 2003. Loss of MCT1, MCT3 and MCT4 expression in the retinal pigment epithelium and neural retina of the 5A11/basigin-null mouse. Invest. Ophthalmol. Vis. Sci. 44(3):1305-1311.
Pisoni, R.L., and Thoene, J.G. 1989. Detection and characterization of a nucleoside trans-port system in human fibroblast lysosomes. J. Biol. Chem. 264:4850-4856.
Plagemann, P.G., and Aran, J.M. 1990. Characterization of Na+-dependent, active nucle-oside transport in rat and mouse peritoneal macrophages, a mouse macrophage cell line and normal rat kidney cells. Biochim. Biophys. Acta 1028:289-298.
Pons, R., Carrozzo, R., Tein, I., Walker, W.F., Addonizio, L.J., Rhead, W., Miranda, A.F., Dimauro, S., and De Vivo, D.C. 1997. Deficient muscle carnitine transport in primary carnitine deficiency. Pediatr. Res. 42:583-587.
Poole, R.C., and Halestrap, A.P. 1993. Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am. J. Physiol. 264:C761-C782.
Poole, R.C., Sansom, C.E., and Halestrap, A.P. 1996. Studies of the membrane topology of the rat erythrocyte H+/lactate cotransporter (MCT1). Biochem. J. 320:817-824.
Pressacco, J., Wiley, J.S., Jamieson, G.P., Erlichman, C., and Hedley, D.W. 1995. Modu-lation of the equilibrative nucleoside transporter by inhibitors of DNA-synthesis. Br. J. Cancer 72:939-942.
Price, N.T., Jackson, V.N., and Halestrap, A.P. 1998. Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past. Biochem. J. 329(Pt 2):321-328.
Prime-Chapman, H.M., Fearn, R.A., Cooper, A.E., Moore, V., and Hirst, B.H. 2004. Differential multidrug resistance-associated protein 1 through 6 isoform expression and function in human intestinal epithelial Caco-2 cells. J. Pharmacol. Exp. Ther. 311 (2):476-484.
Pulaski, L., Kania, K., Ratajewski, M., Uchiumi, T., Kuwano, M., and Bartosz, G. 2005. Differential regulation of the human MRP2 and MRP3 gene expression by glucocorticoids. J. Steroid Biochem. Mol. Biol. 96(3-4):229-234.
Rabindran, S.K., He, H., Singh, M., Brown, E., Collins, K.I., Annable, T., and Greenberger, L.M. 1998. Reversal of a novel multidrug resistance mechanism in human colon carcinoma cells by fumitremorgin C. Cancer Res. 58(24):5850-5858.
Rahman, B., Schneider, H.P., Broer, A., Beitmer, J.W., and Broer, S. (1999). Helix 8 and helix 10 are involved in substrate recognition in the rat monocarboxylate transporter MCT1. Biochemistry 38:11577-11584.
Rausch-Derra, L.C., Hartley, D.P., Meier, P.J., and Klaassen, C.D. 2001. Differential effects of microsomal enzyme-inducing chemicals on the hepatic expression of rat organic anion transporters, Oatp1 and Oatp2. Hepatology 33:1469-1478.
Reid, G., Wielinga, P., Zelcer, N., De Haas, M., Van Deemter, L., Wijnholds, J., Balzarini, J., and Borst, P. 2003. Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol. Pharmacol. 63 (5):1094-1103.
Ritzel, M.W., Yao, S.Y., Huang, M.Y., Elliott, J.F., Cass, C.E., and Young, J.D. 1997. Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1). Am. J. Physiol. 272:C707-C714.
Ritzel, M.W., Ng, A.M., Yao, S.Y., Graham, K., Loewen, S.K., Smith, K.M., Ritzel, R.G., Mowles, D.A., Carpenter, P., Chen, X.Z., Karpinski, E., Hyde, R.J., Baldwin, S.A., Cass, C.E., and Young, J.D. 2001. Molecular identification and characterization of novel human and mouse concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3) broadly selective for purine and pyrimidine nucleosides (system cib). J. Biol. Chem. 276:2914-2927.
Rome, S., Barbot, L., Windsor, E., Kapel, N., Tricottet, V., Huneau, J.F., Reynes, M., Gobert, J.G., and Tomé , D. 2002. The regionalization of PepT1, NBAT and EAAC1 transporters in the small intestine of rats are uncharged from birth to adulthood. J. Nutr. 132:1009-1011.
Rost, D., Mahner, S., Sugiyama, Y., and Stremmel, W. 2002. Expression and localization of the multidrug resistance-associated protein 3 in rat small and large intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 282(4):G720-G726.
Rost, D., Kopplow, K., Gehrke, S., Mueller, S., Friess, H., Ittrich, C., Mayer, D., and Stiehl, A. 2005. Gender-specific expression of liver organic anion transporters in rat. Eur. J. Clin. Invest. 35:635-643.
Rubin, L.J., Johnson, L.R., Dodam, J.R., Dhalla, A.K., Magliola, L., Laughlin, M.H., and Jones, A.W. 2000. Selective transport of adenosine into porcine coronary smooth muscle. Am. J. Physiol. Heart Circ. Physiol. 279(3):H1397-H1410.
Rubio-Aliaga, I., and Daniel, H. 2002. Mammalian peptide transporters as targets for drug delivery. Trends Pharm. Sci. 23(9):434-440.
Sai, Y., and Tsuji, A. 2004. Transporter-mediated drug delivery: recent progress and experimental approaches. Drug Discov. Today 9:712-720.
Saier, M.H., Jr. 2000. A functional-phylogenetic classification system for transmembrane solute transporters. Microbiol. Mol. Biol. Rev. 64(2):354-411.
Saier, M.H., Jr., Eng, B.H., Fard, S., Garg, J., Haggerty, D.A., Hutchinson, W.J., Jack, D.L., Lai, E.C., Liu, H.J., Nusinew, D.P., Omar, A.M., Pao, S.S., Paulsen, I.T., Quan, J.A., Sliwinski, M., Tseng, T.T., Wachi, S., and Young, G.B. 1999. Phylogenetic characteris-tics of novel transport protein families revealed by genome analyses. Biochim. Biophys. Acta 1422:1-56.
Saito, H., Okuda, M., Terada, T., Sasaki, S., and INRI, K.-I. 1995. Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney. J. Pharmacol. Exp. Ther. 275:1631-1637.
Sakata, K., Yamashita, T., Maeda, M., Moriyama, Y., Shimada, S., and Tohyama, M. 2001. Cloning of a lymphatic peptide/histidine transporter. Biochem. J. 356:53-60.
Sarkadi, B., Ozvegy-Laczka, C., Nemet, K., and Varadi, A. 2004. ABCG2 - a transporter for all seasons. FEBS Lett. 567(1):116-120.
Satlin, L.M., Amin, V., and Wolkoff, A.W. 1997. Organic anion transporting polypeptide mediates organic anion/HCO3-exchange. J. Biol. Chem. 272:26340-26345.
Sawada, K., Terada, T., Saito, H., Hashimoto, Y., and Inui, K. 1999. Effects of glibenclamide on glycylsarcosine transport by the rat peptide transporters PEPT1 and PEPT2. Br. J. Pharmacol. 128(6):1159-1164.
Schaub, T.P., Kartenbeck, J., K önig, J., Vogel, O., Witzgall, R., Kriz, W., and Keppler, D. 1997. Expression of the conjugate export pump encoded by the mrp2 gene in the apical membrane of kidney proximal tubules. J. Am. Soc. Nephrol. 8:1213-1221.
Scheffer, G.L., Maliepaard, M., Pijnenborg, A.C., van Gastelen, M.A., de Jong, M.C., Schroeijers, A.B., van der Kolk, D.M., Allen, J.D., Ross, D.D., van der Valk, P., Dalton, W.S., Schellens, J.H., and Scheper, R.J. 2000. Breast cancer resistance protein is localized at the plasma membrane in mitoxantrone- and topotecan-resistant cell lines. Cancer Res. 60(10):2589-2593.
Scheffer, G.L., Kool, M., De Haas, M., De Vree, J.M., Pijnenborg, A.C., Bosman, D.K., Elferink, R.P., Van Der Valk, P., Borst, P., and Scheper, R.J. 2002. Tissue distribution and induction of human multidrug resistant protein 3. Lab. Invest. 82:193-201.
Schinkel, A.H., and Jonker, J.W. 2003. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv. Drug Deliv. Rev. 55:3-29.
Schrenk, D., Gant, T.W., Preisegger, K.H., Silverman, J.A., Marino, P.A., and Thorgeirsson, S.S. 1993. Induction of multidrug resistance gene expression during cholestasis in rats and nonhuman primates. Hepatology 17:854-860.
Schuster, V.L., Lu, R., Kanai, N., Bao, Y., Rosenberg, S., Prie, D., Ronco, P., and Jennings, M.L. 1996. Cloning of the rabbit homologue of mouse ‘basigin’ and rat ‘OX-47’: kidney cell type-specific expression, and regulation in collecting duct cells. Biochim. Biophys. Acta 1311(1):13-19.
Seelig, A., and Landwojtowicz, E. 2000. Structure-activity relationship of P-glycoprotein substrates and modifiers. Eur. J.Pharm. Sci. 12:31-40.
Sekine, T., Cha, S.H., Tsuda, M., Apiwattanakul, N., Nakajima, N., Kanai, Y., and Endou, H. 1998. Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 429:179-182.
SenGupta, D.J., Lum, P.Y., Lai, Y., Shubochkina, E., Bakken, A.H., Schneider, G., and Unadkat, J.D. 2002. A single glycine mutation in the equilibrative nucleoside trans-porter gene, hENT1, alters nucleoside transport activity and sensitivity to nitrobenzylth-ioinosine. Biochemistry 41:1512-1519.
Shapiro, A.B., Fox, K., Lam, P., and Ling, V. 1999. Stimulation of P-glycoprotein mediated drug transport by prazosin and progesterone. Evidence for a third drug-binding site. Eur. J. Biochem. 259:841-850.
Sharom, F.J. 1997. The P-glycoprotein efflux pump: how does it transport drugs? J. Membr. Biol. 160:161-175.
Shen, H., Smith, D.E., and Brosius, F.C., III. 2001. Developmental expression of PepT1 and PepT2 in rat small intestine, colon, and kidney. Pediatr. Res. 49:789-795.
Shi, X., Bai, S., Ford, A.C., Burk, R.D., Jacquemin, E., Hagenbuch, B., Meier, P.J., and Wolkoff, A.W. 1995. Stable inducible expression of a functional rat liver organic anion transport protein in HeLa cells. J. Biol. Chem. 270:25591-25595.
Shimakura, J., Terada, T., Katsura, T., and Inui, K.I. 2005. Characterization of the Human Peptide Transporter PEPT1 promoter: Sp1 Functions as a Basal Transcriptional Regula-tor of Human PEPT1. Am. J. Physiol. Gastrointest. Liver Physiol. 289(3):G471-G477.
Shiraga, T., Miyamoto, K., Tanaka, H., Yamamoto, H., Taketani, Y., Morita, K., Tamai, I., Tsuji, A., and Takeda, E. 1999. Cellular and molecular mechanism of dietary regulation on rat intestinal H+/peptide transporter PepT1. Gastroenterology 116:354-362.
Shore, P.A., Brodie, B.B., and Hogben, C.A.M. 1957. The gastric secretion of drugs: a pH partition hypothesis. J. Pharmacol. Exp. Ther. 119:361-369.
Shu, C., Shen, H., Hopfer, U., and Smith, D.E. 2001. Mechanism of intestinal absorption and renal reabsorption of an orally active ace inhibitor: uptake and transport of fosinopril in cell cultures. Drug Metab. Dispos. 29(10):1307-1315.
Shu, Y., Leabman, M.K., Feng, B., Mangravite, L.M., Huang, C.C., Stryke, D., Kawamoto, M., Johns, S.J., DeYoung, J., Carlson, E., Ferrin, T.E., Herskowitz, I., and Giacomini, K.M. 2003. Evolutionary conservation predicts function of variants of the human organic cation transporter, OCT1. Proc. Natl Acad. Sci. USA 100:5902-5907.
Sikic, B.I. 1997. Pharmacologic approaches to reversing multidrug resistance. Semin Hematol. 34(4 Suppl 5):40-47.
Simon, F.R., Fortune, J., Iwahashi, M., Bowman, S., Wolkoff, A., and Sutherland, E. 1999. Characterization of the mechanisms involved in the gender differences in hepatic taurocholate uptake. Am. J. Physiol. 276:G556-G565.
Slitt, A.L., Cherrington, N.J., Hartley, D.P., Leazer, T.M., and Klaassen, C.D. 2002. Tissue distribution and renal developmental changes in rat organic cation transporter mRNA levels. Drug Metab. Dispos. 30:212-219.
Smit, J.J., Schinkel, A.H., Oude, R.P., Groen, A.K., Wagenaar, E., van, D.L., Mol, C.A., Ottenhoff, R., van der Lugt, N.M., and van Roon, M.A. 1993. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75(3):451-462.
Soler, C., Felipe, A., Mata, J.F., Casado, F.J., Celada, A., and Pastor-Anglada, M. 1998. Regulation of nucleoside transport by lipopolysaccharide, phobol esters, and tumor necrosis factor-alpha in human B-lymphocytes. J. Biol. Chem. 273:26939-26945.
Soler, A.P., Gilliard, G., Xiong, Y., Knudsen, K.A., Martin, J.L., DeSuarez, G.B., Mota Gamboa, J.D., Mosca, W., and Zoppi, L.B. 2001. Overexpression of neural cell adhesion molecule in Chagas’ myocarditis. Hum. Pathol. 32:149-155.
Song, X., Lorenzi, P.L., Landowski, C.P., Vig, B.S., Hilfinger, J.M., and Amidon, G.L. 2005. Amino acid ester prodrugs of the anticancer agent gemcitabine: synthesis, bioconversion, metabolic bioevasion, and hPEPT1-mediated transport. Mol. Pharm. 2 (2):157-167.
Sorensen, M., Steenberg, B., Knipp, G.T., Wang, W., Steffansen, B., Frokjaer, S., and Borchardt, R.T. 1997. The effect of beta-turn structure on the permeation of pep-tides across monolayers of bovine brain microvessel endothelial cells. Pharm. Res. 14 (10):1341-1348.
Soul-Lawton, J., Seaber, E., On, N., Wootton, R., Rolan, P., and Posner, J. 1995. Absolute bioavailability and metabolic disposition of valaciclovir, the L-valyl ester of aciclovir, following oral administration to humans. Antimicrob. Agents Chemother. 39:2759-2764.
Spahn-Langguth, H., and Langguth, P. 2001. Grapefruit juice enhances intestinal absorp-tion of the P-glycoprotein substrate talinolol. Eur. J. Pharm. Sci. 12(4):361-367.
Stanley, C.A., DeLeeuw, S., Coates, P.M., Vianey-Liaud, C., Divry, P., Bonnefont, J.P., Saudubray, J.M., Haymond, M., Trefz, F.K., Breningstall, G.N., Wappner, R.S., Byrd, D.J., Sansaricq, C., Tein, I., Grover, W., Valle, D., Rutledge, S.L., and Treem, W.R. 1991. Chronic cardiomyopathy and weakness or acute coma. Ann. Neurol. 30 (5):709-716.
Staud, F., and Pavek, P. 2005. Breast cancer resistance protein (BCRP/ABCG2). Int. J. Biochem. Cell. Biol. 37(4):720-725.
Staudinger, J.L., Goodwin, B., Jones, S.A., Hawkins-Brown, D., MacKenzie, K.I., LaTour, A., Liu, Y., Klaassen, C.D., Brown, K.K., Reinhard, J., Willson, T.M., Koller, B.H., and Kliewe, S.A. 2001. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl Acad. Sci. USA 98:3369-3374.
Steffansen, B., Nielsen, C.U., Brodin, B., Eriksson, A.H., Andersen, R., and Frokjaer, S. 2004. Intestinal solute carriers: an overview of trends and strategies for improving oral drug absorption. Eur. J. Pharm. Sci. 21:3-16.
Steffansen, B., Nielsen, C.U., and Frokjaer, S. 2005. Delivery aspects of small peptides and substrates for peptide transporters. Eur. J. Pharm. Biopharm. 60(2):241-245.
Steiner, H.Y., Naider, F., and Becker, J.M. 1995. The PTR family: a new group of peptide transporters. Mol. Microbiol. 16:825-834.
Steingrimsdottir, H., Gruber, A., Palm, C., Grimfors, G., Kalin, M., and Eksborg, S. 2000. Bioavailability of aciclovir after oral administration of aciclovir and its prodrug valaci-clovir to patients with leukopenia after chemotherapy. Antimicrob. Agents Chemother. 44 (1):207-209.
Stewart, B.H., Chan, O.H., Jezyk, N., and Fleisher, D. 1997. Discrimination between drug candidates using models for evaluation of intestinal absorption. Adv. Drug Deliv. Rev. 23 (1):27-45.
Strausberg, R.L., Feingold, E.A., Grouse, L.H., Derge, J.G., Klausner, R.D., Collins, F.S., Wagner, L., Shenmen, C.M., Schuler, G.D., Altschul, S.F., Zeeberg, B., Buetow, K.H., Schaefer, C.F., Bhat, N.K., Hopkins, R.F., Jordan, H., Moore, T., Max, S.I., Wang, J., Hsieh, F., Diatchenko, L., Marusina, K., Farmer, A.A., Rubin, G.M., Hong, L., Stapleton, M., Soares, M.B., Bonaldo, M.F., Casavant, T.L., Scheetz, T.E., Brownstein, M.J., Usdin, T.B., Toshiyuki, S., Carninci, P., Prange, C., Raha, S.S., Loquellano, N.A., Peters, G.J., Abramson, R.D., Mullahy, S.J., Bosak, S.A., McEwan, P.J., McKernan, K.J., Malek, J.A., Gunaratne, P.H., Richards, S., Worley, K.C., Hale, S., Garcia, A.M., Gay, L.J., Hulyk, S.W., Villalon, D.K., Muzny, D.M., Sodergren, .J., Lu, X., Gibbs, R.A., Fahey, J., Helton, E., Ketteman, M., Madan, A., Rodrigues, S., Sanchez, A., Whiting, M., Young, A.C., Shevchenko, Y., Bouffard, G.G., Blakesley, R.W., Touchman, J.W., Green, E.D., Dickson, M.C., Rodriguez, A.C., Grimwood, J., Schmutz, J., Myers, R.M., Butterfield, Y.S., Krzywinski, M.I., Skalska, U., Smailus, D.E., Schnerch, A., Schein, J.E., Jones, S.J., and Marra, M.A. (2002). Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc. Natl Acad. Sci. USA 99(26):16899-16903.
Sugawara, I., Kataoka, I., Morishita, Y., Hamada, H., Tsuruo, T., Itoyama, S., and Mori, S. 1988. Tissue distribution of P-glycoprotein encoded by a multidrug-resistant gene as revealed by a monoclonal antibody, MRK 16. Cancer Res. 48(7):1926-1929.
Sugawara, M., Huang, W., Fei, Y.J., Leibach, F.H., Ganapathy, V., and Ganapathy, M.E. 2000. Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J. Pharm. Sci. 89(6):781-789.
Sun, D., Landowski, C.P., Chu, X., Wallsten, R., Fleisher, D., and Amidon, G.L. 2001. Drug inhibition of Gly-Sar uptake and hPepT1 localization using hPepT1-GFP fusion protein. AAPS PharmSci 3:Article 2.
Sun, D., Yu, L.X., Hussain, M.A., Wall, D.A., Smith, R.L., and Amidon, G.L. 2004. In vitro testing of drug absorption for drug ‘developability’ assessment: forming an inter-face between in vitro preclinical data and clinical outcome. Curr. Opin. Drug Discov. Devel. 7(1):75-85.
Sundaram, M., Yao, S.Y., Ng, A.M., Cass, C.E., Baldwin, S.A., and Young, J.D. 2001. Equilibrative nucleoside transporters: mapping regions of interaction for the substrate analogue nitrobenzylthioinosine (NBMPR) using rat chimeric proteins. Biochemistry 40 (27):8146-8151.
Suzuki, H., and Sugiyama, Y. 1998. Excretion of GSSG and glutathione conjugates mediated by MRP1 and cMOAT/MRP2. Semin. Liver Dis. 18(4):359-376.
Suzuki, H., and Sugiyama, Y. 1999. Transporters for bile acids and organic anions. Pharm. Biotechnol. 12:387-439.
Swaan, P.W., and Tukker, J.J. 1997. Molecular determinants of recognition for the intesti-nal peptide carrier. J. Pharm. Sci. 86:596-602.
Taipalensuu, J., Tornblom, H., Lindberg, G., Einarsson, C., Sjoqvist, F., Melhus, H., Garberg, P., Sjostrom, B., Lundgren, B., and Artursson, P. 2001. Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers. J. Pharmacol. Exp. Ther. 299:164-170.
Takahashi, K., Masuda, S., Nakamura, N., Saito, H., Futami, T., Doi, T., and Inui, K.-I. 2001. Upregulation of the H+-peptide cotransporter PepT2 in rat remnant kidney. Am. J. Physiol. Renal Physiol. 281:F1109-F1116.
Tamai, I., Yabuuchi, H., Nezu, J., Sai, Y., Oku, A., Shimane, M., and Tsuji, A. 1997. Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. FEBS Lett. 419:107-111.
Tamai, I., Ohashi, R., Nezu, J.I., Yabuuchi, H., Oku, A., Shimane, M., Sai, Y., and Tsuji, A. 1998. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J. Biol. Chem. 273:20378-20382.
Tamai, I., Nezu, J., Uchino, H., Sai, Y., Oku, A., Shimane, M., and Tsuji, A. 2000a. Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem. Biophys. Res. Commun. 273:251-260.
Tamai, I., Ohashi, R., Nezu, J.I., Sai, Y., Kobayashi, D., Oku, A., Shimane, M., and Tsuji, A. (2000b). Molecular and functional characterization of organic cation/carnitine transporter family in mice. J. Biol. Chem. 275:40064-40072.
Tamai, I., China, K., Sai, Y., Kobayashi, D., Nezu, J.I., Kawahara, E., and Tsuji, A. 2001. Na(+)-coupled transport of L-carnitine via high-affinity carnitine transporter OCTN2 and its subcellular localization in kidney. Biochim. Biophys. Acta 1512:273-284.
Tanaka, H., Miyamoto, K.-I., Morita, K., Haga, H., Segawa, H., Shiraga, T., Fujioka, A., Kouda, T., Taketani, Y., Hisano, S., Fukiji, Y., Kitagawa, K., and Takeda, E. 1998. Regulation of the PepT1 peptide transporter in the rat small intestine in response to 5-fluorouracil-induced injury. Gastroenterology 114:714-723.
Tanaka, T., Uchiumi, T., Hinoshita, E., Inokuchi, A., Toh, S., Wada, M., Takano, H., Kohno, K., and Kuwano, M. 1999. The human multidrug resistance protein 2 gene: functional characterization of the 5-flanking region and expression in hepatic cells. Hepatology 30:1507-1712.
Tein, I. 2003. Carnitine transport: pathophysiology and metabolism of known molecular defects. J. Inherit. Metab. Dis. 26:147-169.
Tein, I., De Vivo, D.C., Bierman, F., Pulver, P., De Meirleir, L.J., Cvitanovic-Sojat, L., Pagon, R.A., Bertini, E., Dionisi-Vici, C., Servidei, S., and DiMauro, S. 1990. Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy. Pediatr. Res. 28:247-255.
Temple, C.S., Bronk, J.K., Bailey, P.D., and Boyd, C.A. 1995. Substrate charge dependence of stoichiometry shows membrane potential is driving force for proton-peptide cotransport in rat renal cortex. Pflugers Arch. Eur. J. Physiol. 430:825-829.
Temple, C.S., Bailey, P.D., Bronk, J.R., and Boyd, C.A.R. 1996. A model for the kinetics of neutral and anionic dipeptide-proton cotransport by the apical membrane of rat kidney cortex. J. Physiol. 494(Pt 3):795-808.
Terada, T., Sawada, K., Saito, H., Hashimoto, Y., and Inui, K.-I. 1999. Functional charac-teristics of basolateral peptide transporter in the human intestinal cell line Caco-2. Am. J. Physiol. 276:G1435-G1441.
Terada, T., Saito, H., Sawada, K., Hashimoto, Y., and Inui, K.-I. 2000a. N-terminal halves of rat H+/peptide transporters are responsible for their substrate recognition. Pharm. Res. 17:15-20.
Terada, T., Sawada, K., Tatsuya, I., Saito, H., Hashimoto, Y., and Inui, K.-I. 2000b. Functional expression of novel peptide transporter in renal basolateral membranes. Am. J. Physiol. Renal. Physiol. 279:F851-F857.
Terao, T., Hisanaga, E., Sai, Y., Tamai, I., and Tsuji, A. 1996. Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as an absorption barrier. J. Pharm. Pharmacol. 48(10):1083-1089.
Thamotharan, M., Bawani, S.Z., Zhou, X., and Adibi, S.A. 1998. Mechanism of dipeptide stimulation of its own transport in a human intestinal cell line. Proc. Assoc. Am. Physicians 110:361-368.
Thamotharan, M., Bawani, S.Z., Zhou, X., and Adibi, S.A. 1999a. Functional and molecular expression of intestinal oligopeptide transporter (PepT-1) after a brief fast. Metabolism 48:681-684.
Thamotharan, M., Bawani, S.Z., Zhou, X., and Adibi, S.A. 1999b. Hormonal regulation of oligopeptide transporter pept-1 in a human intestinal cell line. Am J. Physiol. 276:C821-C826.
Theis, S., Doring, F., and Daniel, H. 2001. Expression of the myc/His-tagged human peptide transporter hPepT1 in yeast for protein purification and functional analysis. Protein Exp. Purif. 22:436-442.
Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M.M., Pastan, I., and Willingham, M.C. 1987. Cellular localization of the multidrug resistance gene product P-glycoprotein in normal human tissues. Proc. Natl Acad. Sci. USA 84:7735-7738.
Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M.M., Pastan, I., and Willingham, M.C. 1989. Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and cross-reactivity of one antibody with a muscle protein. J. Histochem. Cytochem. 37(2):159-164.
Tian, Q., Zhang, J., Tan, T.M., Chan, E., Duan, W., Chan, S.Y., Boelsterli, U.A., Ho, P.C., Yang, H., Bian, J.S., Huang, M., Zhu, Y.Z., Xiong, W., Li, X., and Zhou, S. (2005). Human multidrug resistance associated protein 4 confers resistance to camptothecins. Pharm. Res. 22(11):1837-1853;
Tirona, R.G., and Kim, R.B. 2002. Pharmacogenomics of organic anion-transporting polypeptides (OATP). Adv. Drug Deliv. Rev. 54:1343-1352.
Tirona, R.G., Leake, B.F., Merino, G., and Kim, R.B. 2001. Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. J. Biol. Chem. 276:35669-35675.
Torok, M., Gutmann, H., Fricker, G., and Drewe, J. 1999. Sister of P-gp expression in different tissues. Biochem. Pharmacol. 57(7):833-835.
Torok, H.P., Glas, J., Tonenchi, L., Lohse, P., Muller-Myhsok, B., Limbersky, O., Neugebauer, C., Schnitzler, F., Seiderer, J., Tillack, C., Brand, S., Brunnler, G., Jagiello, P., Epplen, J.T., Griga, T., Klein, W., Schiemann, U., Folwaczny, M., Ochsenkuhn, T., and Folwaczny, C. 2005. Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn’s disease. Gut 54:1421-1427.
Tortora, G.J., and Grabowski., S.R. 1993. Principles of Anatomy and Physiology, Harper Collins College Publishers, New York, p. 768.
Triscari, J., O’Donnell, D., Zinny, M., and Pan, H.Y. 1995. Gastrointestinal absorption of pravastatin in healthy subjects. J. Clin. Pharmacol. 35:142-144.
Trompier, D., Baubichon-Cortay, H., Chang, X.B., Maitrejean, M., Barron, D., Riordon, J.R., and Di Pietro, A. 2003. Multiple flavonoid-binding sites within multidrug resistance protein MRP1. Cell Mol. Life Sci. 60:2164-2177.
Urakami, Y., Nakamura, N., Takahashi, K., Okuda, M., Saito, H., Hashimoto, Y., and Inui, K. 1999. Gender differences in expression of organic cation transporter OCT2 in rat kidney. FEBS Lett. 461(3):339-342.
Urakami, Y., Okuda, M., Saito, H., and Inui, K. 2000. Hormonal regulation of organic cation transporter OCT2 expression in rat kidney. FEBS Lett. 473(2):173-176.
Utoguchi, N., and Audus, L.L. 2000. Carrier-mediated transport of valproic acid in BeWo cells, a human trophoblast cell line. Int. J. Pharm. 195:115-124.
Vaidyanathan, J.B., and Walle, T. 2001. Transport and metabolism of the tea flavonoid (−)-epicatechin by the human intestinal cell line Caco-2. Pharm. Res.18(10): 1420-1425.
Valdes, R., Ortega, M.A., Casado, F.J., Felipe, A., Gil, A., Sanchez-Pozo, A., and Pastor-Anglada, M. 2000. Nutritional regulation of nucleoside transporter expression in rat small intestine. Gastroenterology 119:1623-1630.
Valdes, R., Casado, F.J., and Pastor-Anglada, M. 2002. Cell-cycle-dependent regula-tion of CNT1, a concentrative nucleoside transporter involved in the uptake of cell-cycle-dependent nucleoside-derived anticancer drugs. Biochem. Biophys. Res. Commun. 296:575-579.
Van, L., Pan, Y.X., Bloomquist, J.R., Webb, K.E., Jr., and Wong, E.A. 2005. Developmen-tal regulation of a turkey intestinal peptide transporter (PepT1). Poult. Sci. 84(1):75-82.
Van Aubel, R.A., Hartog, A., Bindels, R.J., Van Os, C.H., and Russel, F.G. 2000. Expres-sion and immunolocalization of multidrug resistance protein 2 in rabbit small intestine. Eur. J. Pharmacol. 400(2-3):195-198.
Van Aubel, R.A., Smeets, P.H., Peters, J.G., Bindels, R.J., and Russel, F.G. 2002. The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kid-ney proximal tubules: putative efflux pump for urinary cAMP and cGMP. J. Am. Soc. Nephrol. 13:595-603.
Velpandian, T., Jasuja, R., Bhardwaj, R.K., Jaiswal, J., and Gupta, S.K. 2001. Piperine in food: interference in the pharmacokinetics of phenytoin. Eur. J. Drug Metab. Pharmacokinit. 26:241-247.
Vickers, M.F., Mani, R.S., Sundaram, M., Hogue, D.L., Young, J.D., Baldwin, S.A., and Cass, C.E. 1999. Functional production and reconstitution of the human equilibrative nucleoside transporter (hENT1) in Saccharomyces cerevisiae. Interaction of inhibitors of nucleoside transport with recombinant hENT1 and a glycosylation-defective derivative (hENT1/N48Q). Biochem. J. 339(1):21-32.
Vickers, M.F., Kumar, R., Visser, F., Zhang, J., Charania, J., Raborn, R.T., Baldwin, S.A., Young, J.D., and Cass, C.E. 2002. Comparison of the interaction of uridine, cytidine, and other pyrimidine nucleoside analogs with recombinant human equilibrative nucleo-side transporter 2 (hENT2) produced in Saccharomyces cerevisiae. Biochem. Cell. Biol. 80 (5):639-644.
Vig, B.S., Lorenzi, P.J., Mittal, S., Landowski, C.P., Shin, H.C., Mosberg, H.I., Hilfinger, J.M., and Amidon, G.L. 2003. Amino acid ester prodrugs of floxuridine: synthesis and effects of structure, stereochemistry, and site of esterification on the rate of hydrolysis. Pharm. Res. 20(9):1381-1388.
Vijayalakshmi, D., and Belt, J.A. 1988. Sodium-dependent nucleoside transport in mouse intestinal epithelial cells. Two transport systems with differing substrate specificities. J. Biol. Chem. 263:19419-19423.
Visser, F., Vickers, M.F., Ng, A.M., Baldwin, S.A., Young, J.D., and Cass, C.E. 2002. Mutation of residue 33 of human equilibrative nucleoside transporters 1 and 2 alters sen-sitivity to inhibition of transport by dilazep and dipyridamole. J. Biol. Chem. 277:395-401.
Wagner, C.A., L ükewille, U., Kaltenbach, S., Moschen, I., Broer, A., Risler, T., Broer, S., and Lang, F. 2000. Functional and pharmacological characterization of the human Na+/carnitine cotransporter hOCTN2. Am. J. Physiol. Renal. Physiol. 279:F584-F591.
Walker, D., Thwaites, D.T., Simmons, N.L., Gilbert, H.J., and Hirst, B.H. 1998. Sub-strate upregulation of the human small intestinal peptide transporter, hPepT1. J. Physiol. 507:697-706.
Walters, H.C., Craddock, A.L., Fusegawa, H., Willingham, M.C., and Dawson, P.A. 2000. Expression, transport properties, and chromosomal location of organic anion transporter subtype 3. Am. J. Physiol. Gastrointest. Liver Physiol. 279:G1188-G1200.
Walter-Sack, I., and Klotz, U. 1996. Influence of diet and nutritional status on drug metabolism. Clin. Pharmacokinet. 31(1):47-64.
Wang, J., and Giacomini, K.M. 1999. Serine 318 is essential for the pyrimidine selectivity of the N2 Na+-nucleoside transporter. J. Biol. Chem. 274:2298-2302.
Wang, J., Su, S.F., Dresser, M.J., Schaner, M.E., Wahington, C.B., and Giacomini, K.M. 1997. Na+-dependent purine nucleoside transporter from human kidney: cloning and functional characterization. Am. J. Physiol. 273:F1058-F1065.
Wang, D.S., Jonker, J.W., Kato, Y., Kusuhara, H., Schinkel, A.H., and Sugiyama, Y. 2002. Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J. Pharmacol. Exp. Ther. 302:510-515.
Wang, D.S., Kusuhara, H., Kato, Y., Jonker, J.W., Schinkel, A.H., and Sugiyama, Y. 2003. Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin. Mol. Pharmacol. 63:844-888.
Wang, Q., Bhardwaj, R.K., Herrera-Ruiz, D., Hanna, N.N., Gudmundsson, O.S., Buranachokpaisan, T., Hidalgo, I.J., and Knipp, G.T. 2004. Expression of multiple drug resistance conferring proteins in normal Chinese and Caucasian small and large intestinal tissue samples. Mol. Pharm. 1(6):447-454.
Ward, J.L., Leung, G.P.H., Toan, S.V., and Tse, C.M. 2003. Functional analysis of sitedirected glycosylation mutants of the human equilibrative nucleoside transporter-2. Arch. Biochem. Biophys. 411(1):19-26.
Watanabe, K., Sawano, T., Jinriki, T., and Sato, J. 2004. Studies on intestinal absorption of sulpiride (3): intestinal absorption of sulpiride in rats. Biol. Pharm. Bull. 27:77-81.
van de Waterbeemd, H. 2002. High-throughput and in silico techniques in drug meta-bolism and pharmacokinetics. Curr. Opin. Drug Discov. Devel. 5(1):33-43.
Watkins, P.B. 1997. The barrier function of CYP3A4 and P-glycoprotein in the small bowel. Adv. Drug Deliv. Rev. 27:161-170.
Weller, S., Blum, M., Doucette, M., Burnette, T., Cederberg, D.M., de Miranda, P., and Smiley, M.L. 1993. Pharmacokinetics of the aciclovir pro-drug valaciclovir after esca-lating single- and multiple-dose administration to normal volunteers. Clin. Pharmacol. Ther. 54:595-605.
Wenzel, U., Gebert, I., Weintraut, H., Weber, W.M., Clauss, W., and Daniel, H. 1996. Transport characteristics of differently charged cephalosporin antibiotics in oocytes expressing the cloned intestinal peptide transporter PepT1 and in human intestinal Caco-2 cells. J. Pharmacol. Exp. Ther. 277(2):831-839.
Wenzel, U., Diehl, D., Herget, M., Kuntz, S., and Daniel, H. 1999. Regulation of the high-affinity H+/peptide cotransporter in renal LLC-PK1 cells. J. Cell. Physiol. 178:341-348.
Wenzel, U., Kuntz, S., Diestel, S., and Daniel, H. 2002. PepT1-mediated cefixime uptake into human intestinal epithelial cells is increased by Ca2+ channels blockers. Antimicrob. Agents. Chemother. 46:1375-1380.
Wielinga, P.R., Reid, G., Challa, E.E., van der Heijden, I., van Deemter, L., de Haas, M., Mol, C., Kuil, A.J., Groeneveld, E., Schuetz, J.D., Brouwer, C., De Abreu, R.A., Wijnholds, J., Beijnen, J.H., and Borst, P. 2002. Thiopurine metabolism and identi-fication of the thiopurine metabolites transported by MRP4 and MRP5 overexpressed in human embryonic kidney cells. Mol. Pharmacol. 62:1321-1331.
Wijnholds, J., Mol, C.A., van Deemter, L., de Haas, M., Scheffer, G.L., Baas, F., Beijnen, J.H., Scheper, R.J., Hatse, S., De Clercq, E., Balzarini, J., and Borst, P. (2000).Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc. Natl Acad. Sci. USA 97:7476-7481.
Williams, J.B., Rexer, B., Sirripurapu, S., John, S., Goldstein, R., Phillips, J.A., Haley, L.L., Sait, N., Shows, T.B., Smith, C.M., and Gerhard, D.S. 1997. The human HNP36 gene is localized to chromosome 11q13 and produces alternative transcripts that are not mutated in multiple endocrine neoplasia, type 1 (MEN I) syndrome. Genomics 42(2):325-330.
Wu, X., Yuan, G., Brett, C.M., Hui, A.C., and Giacomini, K.M. 1992. Sodium-dependent nucleoside transport in choroids plexus from rabbit. Evidence for a single transporter for purine and pyrimidine nucleosides. J. Biol. Chem. 267:8813-8818.
Wu, X., Prasad, P.D., Leibach, F.H., and Ganapathy, V. (1998). cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem. Biophys. Res. Commun. 246:589-595.
Wu, X., Huang, W., Prasad, P.D., Seth, P., Rajan, D.P., Leibach, F.H., Chen, J., Conway, S.J., and Ganapathy, V. 1999. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J. Pharmacol. Exp. Ther. 290:1482-1492.
Wu, X., George, R.L., Huang, W., Wang, H., Conway, S.J., Leibach, F.H., and Ganapathy, V. 2000a. Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim. Biophys. Acta 1466:315-327.
Wu, X., Huang, W., Ganapathy, M.E., Wang, H., Kekuda, R., Conway, S.J., Leibach, F.H., and Ganapathy, V. 2000b. Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am. J. Physiol. Renal. Physiol 279:F449-F458.
Wu, X.C., Whitfield, L.R., and Stewart, B.H. 2000c. Atorvastatin transport in the Caco- 2 cell model: contributions of P-glycoprotein and the proton-monocarboxylic acid cotransporter. Pharm. Res. 17:209-215.
Xia, C.Q., Liu, N., Yang, D., Miwa, G., and Gan, L.S. 2005. Expression, localization, and functional characteristics of breast cancer resistance protein in Caco-2 cells. Drug Metab. Dispos. 33(5):637-643.
Xie, W., Radominska-Pandya, A., Shi, Y., Simon, C.M., Nelson, M.C., Ong, E.S., Waxman, D.J., and Evans, R.M. 2001. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc. Natl Acad. Sci. USA 98:3375-3380.
Xu, J., Liu, Y., Yang, Y., Bates, S., and Zhang, J.T. 2004. Characterization of oligomeric human half-ABC transporter ATP-binding cassette G2. J. Biol. Chem. 279:19781-19789.
Yabuuchi, H., Shimizu, H., Takayanagi, S., and Ishikawa, T. 2001. Multiple splicing variants of two new human ATP-binding cassette transporters, ABCC11 and ABCC12. Biochem. Biophys. Res. Commun. 288(4):933-999.
Yamashita, T., Shimada, S., Guo, W., Sato, K., Kohmura, E., Hayakawa, T., Takagi, T., and Tohyama, M. 1997. Cloning and functional expression of a brain peptide/histidine transporter. J. Biol. Chem. 272:10205-10211.
Yang, C.Y. (1998). Studies on the human intestinal di-/tripeptide transporter HPT-1 as a potential carrier for orally administered drugs. Thesis, Purdue University.
Yang, C.Y., Dantzing, A.H., and Pidgeon, C. (1999). Intestinal peptide transport of systems and oral drug availability. Pharm. Res. 16:1331-1343.
Yao, S.Y., Ng, A.M., Muzyka, W.R., Griffiths, M., Cass, C.E., Baldwin, S.A., and Young, J.D. 1997. Molecular cloning and functional characterization of nitrobenzylth-ioinosine (NBMPR)-sensitive (es) and NBMPR-insensitive (ei) equilibrative nucleoside transporter proteins (rENT1 and rENT2) from rat tissues. J. Biol. Chem. 272(45):28423-28430.
Yao, S.Y., Ng, A.M., Sundaram, M., Cass, C.E., Baldwin, S.A., and Young, J.D. 2001a. Transport of antiviral 3′ -deoxy-nucloside drugs by recombinant human and rat equi-librative, nitriobenzylthioinosine (NBMPR)-insensitive (ENT2) nucleoside transporter proteins produced in Xenopus oocytes. Mol. Membr. Biol. 18:161-167.
Yao, S.Y., Sundaram, M., Chomey, E.G., Cass, E.E., Baldwin, S.A., and Young, J.D. 2001b. Identification of Cys140 in helix 4 as an exofacial cysteine residue within the substrate-translocation channel of rat equilibrative nitrobenzylthioinosine (NBMPR)-insensitive nucleoside transporter rENT2. Biochem. J. 353(Pt 2):387-393.
Yao, W.Y., Ng, A.M., Vickers, M.F., Sundaram, M., Cass, C.E., Baldwin, S.A., and Young, J.D. (2002). Functional and molecular characterization of nucleobase transport by recombinant human and rat equilibrative nucleoside transporters 1 and 2. Chimeric. constructs reveal a role for the ENT2 helix 5-6 region in nucleobase translocation. J. Biol. Chem. 277:24938-24948.
Yeung, A.K., Basu, S.K., Wu, S., Chu, C., Okamoto, C.T., Hamm-Alvarez, S., von Grafenstein, H., Shen, W.C., Kim, K.J., Bolger, M.B., Haworth, I.S., Ann, D., and Lee,V.H. 1998. Molecular identification of a role for tyrosine 167 in the function of the human intestinal proton-coupled dipeptide transporter (hPepT1). Biochem. Biophys. Res. Commun. 250:103-107.
Yoon, H., Fanelli, A., Grollman, E.F., and Philp, N.J. 1997. Identification of a unique monocaroxylate transporter (MCT3) in retinal pigment epithelium. Biochem. Biophys. Res. Commun. 234:90-94.
You, G. 2004. The role of organic ion transporters in drug disposition: an update. Curr. Drug Metab. 5:55-62.
Zelcer, N., Saeki, T., Reid, G., Beijnen, J.H., and Borst, P. 2001. Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J. Biol. Chem. 276:46400-46407.
Zelcer, N., Reid, G., Wielinga, P., Kuil, A., van der Heijden, I., Schuetz, J.D., and Borst, P. 2003. Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem. J. 371(Pt 2):361-367.
Zeng, H., Liu, G., Rea, P.A., and Kruh, G.D. 2000. Transport of amphipathic anions by human multidrug resistance protein 3. Cancer Res. 60(17):4779-4784.
Zhang, L., Dresser, M.J., Chun, J.K., Babbitt, P.C., and Giacomini, K.M. 1997a. Cloning and functional characterization of a rat renal organic cation transporter isoform (rOCT1A). J. Biol. Chem. 272:16548-16554.
Zhang, L., Dresser, M.J., Gray, A.T., Yost, S.C., Terashita, S., and Giacomini, K.M. 1997b. Cloning and functional expression of a human liver organic cation transporter. Mol. Pharmacol. 51:913-921.
Zhang, L., Schaner, M.E., and Giacomini, K.M. 1998. Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J. Pharmacol. Exp. Ther. 286:354-361.
Zhang, Y., Han, H., Elmquist, W.F., and Miller, D.W. 2000. Expression of various mul-tidrug resistance-associated protein (MRP) homologues in brain microvessel endothelial cells. Brain. Res. 876:148-153.
Zhang, E.Y., Knipp, G.T., Ekins, S., and Swaan, P.W. 2002a. Structural biology and function of solute transporters: implications for identifying and designing substrates. Drug Metab. Rev. 34(4):709-750.
Zhang, E.Y., Mitch, A.P., Cheng, C., Ekis, S., and Swaan, P.W. 2002b. Modeling of active transport systems. Adv. Drug Del. Rev. 54:329-354.
Zhang, E.Y., Fu, D.J., Pak, Y.A., Stewart, T., Mukhopadhyay, N., Wrighton, S.A., and Hillgren, K.M. 2004. Genetic polymorphisms in human proton-dependent dipeptide transporter PEPT1: implications for the functional role of Pro586. J. Pharmacol. Exp. Ther. 310(2):437-445.
Zhao, C., Wilson, M.C., Schuit, F., Halestrap, A.P., and Butter, G.A. 2001. Expression and distribution of lactate/monocarboxylate transporter isoforms in pancreatic islets and the exocrine pancreas. Diabetes 50:361-366.
Zhou, X., Thamotharan, M., Gangopadhyay, A., Serdikoff, C., and Adibi, S.A. 2000. Characterization of an oligopeptide transporter in renal lysosomes. Biochim. Biophys. Acta 1466:372-378.
Ziegler, T.R., Fernandez-Estivariz, C., Gu, L.H., Bazargan, N., Umeakunne, K., Wallace, T.M., Diaz, E.E., Rosado, K.E., Pascal, R.R., Galloway, J.R., Wilcox, J.N., and Leader, L.M. 2002. Distribution of the H+/peptide transporter PepT1 in human intestine: up-regulated expression in the colonic mucosa of patients with short-bowel syndrome. Am. J. Clin. Nutr. 75:922-930.
Zimmermann, C., Gutmann, H., Hruz, P., Gutzwiller, J.P., Beglinger, C., and Drewe, J. 2005. Mapping of multidrug resistance gene 1 and multidrug resistance-associated pro-tein isoform 1 to 5 mRNA expression along the human intestinal tract. Drug Metab. Dispos. 33(2):219-224.
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Bhardwaj, R.K. et al. (2008). IntestinalTransporters in Drug Absorption. In: Krishna, R., Yu, L. (eds) Biopharmaceutics Applications in Drug Development. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-72379-2_7
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