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Organic Anion Transporters

  • Chapter
Membrane Transporters as Drug Targets

Part of the book series: Pharmaceutical Biotechnology ((PBIO,volume 12))

Conclusion

Organic anion transporters were first identified in intestine, liver, and kidney based on extensive studies of membrane transport phenomena mainly of xenobiotics. Recent advances in membrane transport studies with the use of molecular biological approaches have confirmed the participation of such carrier-mediated transport in these tissues and the pharmacological and/or pharmacokinetic relevance of these transporters to the disposition of xenobiotics. Furthermore, the tissue distributions of these transporters suggest the physiological significance of carrier- mediated transport of nutrients, endogenous substrates, and xenobiotics in many tissues in addition to intestine, kidney, and liver. Since at least some of the organic anion transporters probably have physiologically crucial roles, manipulation of drug disposition by utilization of these transporters is expected to be useful for regulating the pharmacokinetics of anionic drugs not only in intestinal absorption and renal and hepatic elimination, but also in distribution into pharmacological target tissues.

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References

  • Abe, T., Kakyo, M., Sakagami, H., Tokui, T., Nishio, T., Tanemoto, M., Nomura, H., Hebert, S. C., Matsuno, S., Kondo, S. and Yawo, H., 1998, Molecular characterization and tissue ditribution of a new organic anion transporter subtype (oatp3) that transport thyroid hormones and taurocholate and comparison with oatp2, J. Biol. Chem. 273: 22395–22401.

    Article  PubMed  CAS  Google Scholar 

  • Alper, S. L., Kopito, R. R., Libresco, S. M., and Lodish, H. E, 1988, Cloning and characterization of a murine band 3-related cDNA from kidney and from a lymphoid cell line, J. Biol. Chem. 263: 17092–17099.

    PubMed  CAS  Google Scholar 

  • Balkovetz, D. F., Leibach, F. H., Mahesh, V. B., and Ganapathy, V., 1988, A proton gradient is the driving force for uphill transport of lactate in human placental brush-border membrane vesicles J. Biol. Chem. 263: 13823–13830.

    PubMed  CAS  Google Scholar 

  • Bergwerk, A. J., Shi, X. Y., Ford, A. C., Kanai, N., Jacquemin, E., Burk, R. D., Bai, S., Novikoff, P. M., Stieger, B., Meier, P. J., Schuster, V. L., and Wolkoff, A. W., 1996, Immunological distribution of an organic anion transporter protein in rat liver and kidney, Am. J. Physiol. 271: G231–G238.

    PubMed  CAS  Google Scholar 

  • Biber, J., Custer, M., Werner, A., Kaissling, B., and Murer, H., 1993, Localization of NaPi-1, a Na/Pi cotransporter, in rabbit kidney proximal tubules, Pflugers Arch. 424: 210–215.

    Article  PubMed  CAS  Google Scholar 

  • Boll, M., Markovich, D., Weber, W.-M., Korter, H., Daniel, H., and Murer, H., 1994, Expression cloning of a cDNA from rabbit small intestine related to proton-coupled transport of peptides, â–¡-lactam antibiotics and ACE-inhibitors, Pflugers Arch. 429: 146–149.

    Article  PubMed  CAS  Google Scholar 

  • Bossuyt, X., Muller, M., Hagenbuch, B. and Meier, P. J., 1996, Polyspecific steroid and drug clearance by an organic anion transporter of mammalian liver, J. Pharmacol. Exp. Ther. 276: 891–896.

    PubMed  CAS  Google Scholar 

  • Busch, A. E., Schuster, A., Waldegger, S., Wagner, C. A., Zempel, G., Broer, S., Biber, J., Murer, H., and Lang, F., 1996, Expression of a renal type I sodium/phosphate transporter (NaPi-1) induces a conductance in Xenopus oocytes permeable for organic and inorganic anions, Proc. Natl. Acad. Sci. USA 93: 5347–5351.

    Article  PubMed  CAS  Google Scholar 

  • Carpenter, L., Poole, R. C., and Halestrap, A. P., 1996, Cloning and sequencing of the mono-carboxylate transporter from mouse Ehrilich Lettre tumor cell confirms its identity as MCT1 and demonstrates that glycosylation is not required for MCT1 function, Biochim. Biophys. Acta 1279: 157–163.

    Article  PubMed  Google Scholar 

  • Chong, S. S., Kozak, C. A., Liu, L., Kristjansson, K., Dunn, S. T., Bourdeau, J. E., and Highes, M. R., 1995, Cloning, genetic mapping, and expression analysis of a mouse renal sodium-dependent phosphate cotransporter, Am. J. Physiol. 268: F1038–F1045.

    PubMed  CAS  Google Scholar 

  • Chow, A., Dobbins, J. W., Aronson, P. S., and Igarashi, P., 1992, cDNA cloning and localization of band 3-related protein from ileum, Am. J. Physiol. 263: G345–G352.

    PubMed  CAS  Google Scholar 

  • Cremer, J. E., Cunningham, J. V., Pardridge, W. M., Braun, L. D., and Oldendorf, W. H., 1979, Kinetics of blood-brain barrier transport of pyruvate, lactate and glucose in sucking, weaning and adult rats, J. Neurochem. 33: 439–445.

    Article  PubMed  CAS  Google Scholar 

  • Dantzler, W. H., and Wright, S. H., 1997, Renal tubular secretion of Organic anions, Adv. Drug Deliv. Rev. 25: 217–230.

    Article  CAS  Google Scholar 

  • Deguchi, Y., Nozawa, K., Yamada, S., Yokoyama, Y., and Kimura, R., 1997, Quantitative evaluation of brain distribution and bloud-brain barrier efflux transport of probenecid in rats by microdialysis: Possible involvement of the monocarboxylic acid transport system, J. Pharmacol. Exp. Ther. 280: 551–560.

    PubMed  CAS  Google Scholar 

  • DeLeve, L. D., and Kaplowitz, N., 1991, Glutathione metabolism and its role in hepatotoxicity, Pharmacol. Ther. 52: 287–305.

    Article  PubMed  CAS  Google Scholar 

  • Demuth, D. R., Showe, L. C., Ballantine, M., Palumbo, A., Fraser, P. J., Cioe., L., Rovera, G., and Curtis, P. J., 1986, Cloning and structural characterization of human non-erythroid band 3-like protein, EMBO J. 5: 1205–1214.

    PubMed  CAS  Google Scholar 

  • de Vries, M. H., Groothuis, G. M. M., Mulder, G. J., Nguyen, H., and Meijer, D. K. F., 1985, Secretion of the organic anion harmol sulfate from liver into blood, Biochem. Pharmacol. 34: 2129–2135.

    Article  PubMed  Google Scholar 

  • Dohgen, M., Hayashi, H., Yajima, T., and Suzuki, T., 1994, Stimulation of bicarbonate secretion by luminal short-chain fatty acids in the rat and human colon in vivo, Japn. J. Physiol. 44: 519–531.

    Article  CAS  Google Scholar 

  • Eckhardt, U., Horz, J. A., Petzinger, E., Stuber, W., Reers, M., Dickneite, G., Daniel, H., Wagener, M., Hagenbuch, B., Stieger, B., and Meier, P. J., 1996, The peptide-based thrombin inhibitor CRC220 is a new substrate of the basolateral rat brain organic anion-transporting polypeptide, Hepatology 24: 380–384.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Fisher, R. B., 1981, Active transport of salicylate by rat jejunum, Q. J. Exp. Physiol. 66: 91–98.

    PubMed  CAS  Google Scholar 

  • Garcia, C. K., Li, X., Luna, J., and Francke, U., 1994, cDNA cloning of the human mono-carboxylate transporter 1 and chromosomal localization of the SLC16A1 locus to 1p13.2-p12, Geomics 23: 500–503.

    CAS  Google Scholar 

  • Garcia, C. K., Brown, M. S., Pathak, R. K., and Goldstein, J. L., 1995, cDNA cloning of MCT2, a second monocarboxylate transporter expressed in different cells than MCT1, J. Biol. Chem. 270: 1843–1849.

    Article  PubMed  CAS  Google Scholar 

  • Gehrig, H., Muller, W., and Appelhans, H., 1992, Complete nucleotide sequence of band 3 related anion transport protein AE2 from human kidney, Biochim. Biophys. Acta 1130: 326–328.

    PubMed  CAS  Google Scholar 

  • Gerhart, D. Z., Enerson, B. E., Zhdankina, O. Y., Leino, R. L., Drewes, L. R., 1997, Expression of monocarboxylate transporter MCT1 by brain endothelium and glia in adult and suckling rats, Am. J. Physiol. 273: E207–E213.

    PubMed  CAS  Google Scholar 

  • Gottesmann, M. M., and Pastan, I., 1993, Biochemistry of multidrug transporter, Annu. Rev. Biochem. 62: 385–427.

    Article  Google Scholar 

  • Hagenbuch, B., and Meier, P. J., 1994, Molecular cloning. Chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter, J. Clin. Invest. 93: 1326–1331.

    Article  PubMed  CAS  Google Scholar 

  • Hagenbuch, B., Steiger, B., Forguet, H., Lubbert, H., and Meier, P. J., 1991, Functional expression cloning and characterization of the hepatic Na+/bile acid cotransport system, Proc. Natl. Acad. Sci. USA 88: 10629–10633.

    Article  PubMed  CAS  Google Scholar 

  • Hagenbuch, B., Scharschmidt, B. F., and Meier, P. J., 1994, Use of antisense oligonucleotides to assess the role of the cloned transporters Ntcp and oatp in a Na+-dependent and Na+-independent hepatic uptake of taurocholate and non-bile acid organic anions, Hepatology 20: 201A.

    Google Scholar 

  • Hagenbuch, B., Stieger, B., Schteingart, C. D., Hofmann, A. F., Wolkoff, A. W., and Meier, P. J., 1995, Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver, Gastroenterology 109: 1274–1282.

    Article  PubMed  Google Scholar 

  • Harig, J. M., Soergel, K. H., Barry, J. A., and Ramaswamy, K., 1991, Transport of propinate by ileal brush-border membrane vesicles, Am. J. Physiol. 260: G776–782.

    PubMed  CAS  Google Scholar 

  • Hunter, J., and Hirst, B. H., 1997, Intestinal secretion of drugs. The role of P-glycoprotein and related efflux systems in limiting oral drug absorption, Adv. Drug Deliv. Rev. 25: 129–157.

    Article  CAS  Google Scholar 

  • Ito, K., Suzuki, H., Hirohashi, T., Kume, K., Shimizu, T. and Sugiyama, Y., 1997, Molecular cloning of canalicular multispecific organic anion transporter defective in EHBR, Am. J. Physiol. 272: G16–G22.

    PubMed  CAS  Google Scholar 

  • Jackson, V. N., Price, N. T., and Halestrap, A. P., 1995, cDNA cloning of MCT1, a monocarboxylate transporter from rat skeletal muscle, Biochim. Biophy.: Acta 1238: 193–196.

    Article  Google Scholar 

  • Jacquemin, E., Hagenbuch, B., Stieger, B., Wolkoff, A. W., and Meier, P. J., 1994, Expression cloning of rat liver Na+-independent organic anion transporter, Proc. Natl. Acad. Sci. USA 91: 133–137.

    Article  PubMed  CAS  Google Scholar 

  • Kakyo, M., Sakagami, H., Nishio, T., Takai, D., Nakagomi, R., Tokui, T., Naitoh, T., Matsuno, S., Abe, T. and Yawo, H., 1999, Immunohistochemical distribution and functional characterization of an organic anion transporting polypeptide 2 (oatp2), FEBS-Lett. 26: 343–346.

    Article  Google Scholar 

  • Kanai, N., Lu, R, Satriano, J. A., Bao, Y., Wolkoff, A. W., and Schuster, V. L., 1995, Identification and characterization of a prostaglandin transporter, Science 268: 866–869.

    Article  PubMed  CAS  Google Scholar 

  • Kanai, N., Lu, R., Bao, Y., Wolkoff, A. W., and Schuster, V. L., 1996, Transient expression of oatp organic anion transporter in mammalian cells: Identification of candidate substrates, Am. J. Physiol. 270: F319–F325.

    PubMed  CAS  Google Scholar 

  • Kelly, R. A., and Smith, T. W., 1992, Recognition and management of digitalis toxicity, Am. J. Cardiol. 69: 108G–119G.

    Article  PubMed  CAS  Google Scholar 

  • Kudrycki, K. E., Newman, P. R., and Shull, G. E., 1990, cDNA cloning and tissue distribution of mRNAs for two proteins that are related to the band 3 Cl-/HCO -3 exchanger, J. Biol. Chem. 265: 462–471.

    PubMed  CAS  Google Scholar 

  • Kullak-Ublick, G. A., Hagenbuch, B., Stieger, B., Schteingart, C. D., Hosmann, A. F., Wolkoff, A. W., and Meier, P. J., 1995, Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver, Gastroenterology 109: 1274–1282.

    Article  PubMed  CAS  Google Scholar 

  • Liang, R., Fei, Y.-J., Presad, 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 locarization, J. Biol. Chem. 270: 6456–6463.

    Article  PubMed  CAS  Google Scholar 

  • Lindsey, A. E., Schneider, K., Simmons, D. M., Baron, R., Lee, B. S., and Kopito, R. R., 1990, Functional expression and subcellular localization of an anion exchanger cloned from choroid plexus, Proc. Natl. Acad. Sci. USA 87: 5278–5282.

    Article  PubMed  CAS  Google Scholar 

  • Lucus, M., 1983, Determination of acid surface pH in vivo in rat proximal jejunum, Gut 24: 734–739.

    Article  Google Scholar 

  • Masuda, S., Saito, H., Nonoguchi, H., Tomita, K., and Inui, K., 1997, mRNA distribution and membrane locarization of the OAT-K1 organic anion transporter in rat renal tubules, FEBS Lett. 407: 127–131.

    Article  PubMed  CAS  Google Scholar 

  • Masuda, S., Ibaramoto, K., Takeuchi, A., Saito, H., Hashimoto, Y. and Inui, K. 1999, Cloning and functional characterization of a new multispecific organic anion transporter, OAT-K2 in rat kidney, Mol. Pharmacol. 55: 743–752.

    PubMed  CAS  Google Scholar 

  • Mayer, U., Wageneaar, E., Beijnen, J. H., Smit, J. W., Meijer, D. K. F., van Asperen, J., Borst, P., and Schinkel, A. H., 1996, Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr l a P-glycoprotein, Br. J. Pharmacol. 119: 1038–1044.

    PubMed  CAS  Google Scholar 

  • McDermott, J. C., and Bonen, A., 1994, Lactate transport in rat sarcolemmal vesicles and intact skeletal muscle, and after muscle contraction, Acta Physiol. Scand. 151: 17–28.

    Article  PubMed  CAS  Google Scholar 

  • Min, A. D., Johansen, K. L., Campell, C. G., and Wolkoff, A. W., 1991, Role of chloride and intracellular pH on the activity of the rat hepatocytes organic anion transporter, J. Clin. Invest. 87: 1496–1502.

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto, K., Shiraga, T., Yamamoto, H., Haga, H., Taketani, Y., Morita, K., Tamai, I., Sai, Y., and Tsuji, A., 1996, Sequence, tissue distribution and developmental changes in rat intestinal oligopeptide transporter, Biochim. Biophys. Acta 1305:34–38.

    PubMed  Google Scholar 

  • Muller, M., and Jansen, P. L., 1997, Molecular aspects of hepatobiliary transport, Am. J. Physiol. 276: G1285–G1303.

    Google Scholar 

  • Nijssen, H. M. J., Pijning, T., Meijer, D. K. F., and Groothuis, G. M. M., 1991, Mechanistic aspects of uptake and sinusoidal efflux of dibromosulfophothalein in the isolated perfused liver, Biochem. Pharmacol. 42: 1997–2002.

    Article  PubMed  CAS  Google Scholar 

  • Noe, B., Hagenbuch, B., Stieger, B., and Meier, P. J., 1997, Isolation of multispecific organic anion and cardiac glycoside transporter from rat brain, Proc. Natl. Acad. Sci. USA 94:10346–10350.

    Article  PubMed  CAS  Google Scholar 

  • Ogihara, T., Tamai, I., and Tsuji, A., 1999, Structural characteriztion of substrates for the anion exchange transporter in Caco-2 cells, Pharm. Res., in press.

    Google Scholar 

  • Oude Elferink, R. P. J., Meier, D. K. F., Kuipers, F., Jansen, P. L. M., Groen, A. K., and Groothuis, G. M. M., 1995, Hepatobiliary secretion of organic compounds; molecular mechanisms of membrane transport, Biochim. Biophys. Acta 1241:215–268.

    PubMed  Google Scholar 

  • Pardridge, W. M., 1983, Brain metabolism: A perspective from the blood-brain barrier, Physiol. Rev. 63: 1481–1535.

    PubMed  CAS  Google Scholar 

  • Pardridge, W. M., 1986, Blood-brain barrier transport of nutrients, Nutr. Rev. 44:15–25.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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: 321–328.

    PubMed  CAS  Google Scholar 

  • Pritchard, J. B., and Miller, D. S., 1993, Mechanisms mediating renal secretion of organic anions and cations, Physiol. Rev. 73:765–796.

    PubMed  CAS  Google Scholar 

  • Proost, J. H., Nijssen, H. M. J., Strating, C. B., Meijer, D. K. F., and Groothuis, G. M. M., 1993, Pharmacokinetic modeling of the sinusoidal efflux of anionic ligands from the isolated perfused rat liver. The influence of albumin, J. Pharmacokinet. Biopharm 21: 375–349.

    Article  PubMed  CAS  Google Scholar 

  • Saito, H., Masuda, S., and Inui, K., 1996, Cloning and functional characterization of a novel rat organic anion transporter mediating basolateral uptake of methotrexate in the kidney, J. Biol. Chem. 271: 26719–20725.

    Google Scholar 

  • Saltin, L. M., Amin, V., and Wolkoff, A. W., 1997, Organic anion transporting polypeptide mediate organic anion/HCO -3 exchange, J. Biol. Chem. 272:26340–26345.

    Article  Google Scholar 

  • Schinkel, A. H., Wagenaar, E., van Deemter, L., Mol, C. A. A. M., and Borst, P., 1995, Absence of the mdr1a P-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A, J. Clin. Invest. 96:1698–1705.

    Article  PubMed  CAS  Google Scholar 

  • Sekine, T., Watanabe, N., Hosoyamada, M., Kanai, Y., and Endou, H., 1997, Expression cloning and characterization of a novel multispecific organic anion transporter, J. Biol. Chem. 272: 18526–18529.

    Article  PubMed  CAS  Google Scholar 

  • Shimada, H., Moewes, B., and Bucrckhardt, G., 1987, Iindirect coupling to Na+ of p-aminohippuric acid uptake into rat renal basolateral membrane vesicles, Am. J. Physiol. 253:F795–F801.

    PubMed  CAS  Google Scholar 

  • Simanjuntak, M. T., Terasaki, T., Tamai, I., and Tsuji, A., 1991, Participation of monocarboxylic anion and bicarbonate exchange system for the transport of acetic acid and monocarboxylic acid drugs in the small intestinal brush-border membrane vesicles, J. Pharmacobio-Dyn. 14:501–508.

    PubMed  CAS  Google Scholar 

  • Takanaga, H., Tamai, I., and Tsuji, A., 1994, pH-dependent and carrier-mediated transport of salicylic acid across Caco-2 cells, J. Pharm, Pharmacol. 46:567–570.

    CAS  Google Scholar 

  • Takanaga, H., Tamai, I., Inaba, S., Sai, Y., Higashida, H., Yamamoto, H., and Tsuji, A., 1995, cDNA cloning and functional characterization of rat intestinal monocarboxylate transporter, Biochem. Biophys. Res. Commun. 217:370–377.

    Article  PubMed  CAS  Google Scholar 

  • Takanaga, H., Maeda, H., Yabuuchi, H. Tamai, I., Higashida, H. and Tsuji, A., 1996, Nicotinic acid transport mediated by pH-dependent anion antiporter and proton cotransporter in rabbit intestinal brush-border membrane, J. Pharm. Pharmacol. 48:1073–1077.

    PubMed  CAS  Google Scholar 

  • Tamai, I., and Tsuji, A., 1987, Transport mechanism of cephalexin in isolated hepatocytes, J. Pharmacobio-Dyn. 10:632–638.

    PubMed  CAS  Google Scholar 

  • Tamai, I., and Tsuji, A., 1996a, Carrier-mediated approaches for oral drug delivery, Adv. Drug Deliv. Rev. 20:5–32.

    Article  CAS  Google Scholar 

  • Tamai, I., and Tsuji, A., 1996b, Drug delivery through the blood-brain barrier, Adv. Drug Deliv. Rev. 19:401–424.

    Article  CAS  Google Scholar 

  • Tamai, I., Maekawa, T., and Tsuji, A., 1990, Membrane potential-dependent and carrier-mediated transport of cefpiramide, a cephalosporin antibiotic, in canalicular rat liver plasma membrane vesicles, J. Pharmacol. Exp. Ther. 253:537–544.

    PubMed  CAS  Google Scholar 

  • Tamai, I., Takanaga, H., Maeda, H., Ogihara, T., Yoneda, M., and Tsuji, A., 1995a, Proton-cotransport of pravastatin across intestinal brush-border membrane, Pharmaceut. Res. 12:1727–1732.

    Article  CAS  Google Scholar 

  • Tamai, I., Takanaga, H., Maeda, H., Sai, Y., Ogihara, T., Higashida, H., and Tsuji, A., 1995b, Participation of a proton-cotransporter, MCT1, in the intestinal transport mechanism for monocarboxylic acids, Biochem. Biophys. Res. Commun. 214: 482–489.

    Article  PubMed  CAS  Google Scholar 

  • Tamai, I., Takanaga, H., Maeda, H., Yabuuchi, H., Sai, Y., Suzuki, Y., and Tsuji, A. 1997, Intestinal brush-border membrane transport of monocarboxylic acids mediated by proton-coupled transport and anion antiport mechanism, J. Pharm. Pharmacol. 49:108–112.

    PubMed  CAS  Google Scholar 

  • Tamai, I., Sai, Y., Ono, A., Kido, Y., Yabuichi, H., T. H., Satoh, E., Ogihara, T., Amano, O., Iseki, S. and Tsuji, A., 1999, Immunohistochemical and functional characterization of pH-dependent intestinal absorption of organic weak acids by monocarboxylic acid transporter MCT1, J. Pharm. Pharmacol. In press.

    Google Scholar 

  • Tiruppathi, C., Balkovetz, D. F., Ganapathy, V., Miyamoto, Y., and Leibach, F. H., 1988, A proton gradient, not a sodium gradient, is the driving force for active transport of lactate in rabbit intestinal brush-border membrane vesicles, Biochem. J. 256:219–223.

    PubMed  CAS  Google Scholar 

  • Tokui, T., Nakai, D., Nakagomi, R., Yawo, H., Suzuki, H., Abe, T. and Sugiyama, Y., 1999, Pravastatin, an HMG-Co A reductase inhibitor, is transported by rat organic anion transporting polypeptide, oatp2. Pharm. Res. 16:904–908.

    Article  PubMed  CAS  Google Scholar 

  • Torres, A. M., Lunazzi, G. C., Stremmel, W., and Tiribelli, C., 1993, Bilitranslocase and sulsobromophthalein-binding protein are both involved in the hepatic uptake of organic anions, Proc. Natl. Acad. Sci. USA 90:8136–8139.

    Article  PubMed  CAS  Google Scholar 

  • Tsuji, A., and Tamai, I., 1996, Carrier-mediated intestinal transport of drugs, Pharmaceut. Res. 13:963–977.

    Article  CAS  Google Scholar 

  • Tsuji, A., and Tamai, I., 1998, Blood-brain barrier transport of drugs, in: An Introduction to the Blood-Brain Barrier (W. M. Pardridge, ed.), Plenum Press, New York, pp. 238–247.

    Google Scholar 

  • Tsuji, A. and Tamai, I., 1999, Carrier-mediated or specialized transport of drugs across the blood-brain barrier, Adv. Drug Deliv. Rev. 36:277–299.

    Article  PubMed  CAS  Google Scholar 

  • Tsuji, A., Terasaki, T., Takanosu, K., Tamai, I., and Nakashima, E., 1986, Uptake of benzylpenicillin, cefpiramide, and cefazolin by freshly prepared rat hepatocytes, Biochem. Pharmacol. 35:151–158.

    Article  PubMed  CAS  Google Scholar 

  • Tsuji, A., Simanjuntak, M. T., Tamai, I., and Terasaki, T., 1990, pH-dependent intestinal transport of monocarboxylic acids: Carrier-mediated and H+-cotransport mechanism versus pH-partition hypothesis, J. Pharmaceut. Sci. 79:1123–1124.

    Article  CAS  Google Scholar 

  • Tsuji, A., Takanaga, H., Tamai, I., and Terasaki, T., 1994, Transcellular transport of benzoic acid across Caco-2 cells by a pH-dependent and carrier-mediated transport mechanism, Pharmaceut. Res. 11: 30–37.

    Article  CAS  Google Scholar 

  • Turner, R. H., Mehta, C. S., and Benet, L. Z., 1970, Apparent directional permeability coefficients for drugs ions: In vitro intestinal perfusion studies, J. Pharm. Sci. 59:590–595.

    Article  PubMed  CAS  Google Scholar 

  • Uchino, H., Tamai, I., Yabuuchi, H., China, K., Miyamato, K., Takeda, E., and Tsuji, A., 1999, Faropenem transport across the renal epithelial luminal membrane via inorganic phosphate transporter Npt1. Antimicrob. Agents Chemother. in press.

    Google Scholar 

  • Werner, A., Moore, M. L., Mantei, N., Biber, J., Semenza, G., and Murer, H., 1991, Cloning and expression of cDNA for a Na/Pi cotransport system of kidney cortex, Proc. Natl. Acad. Sci. USA 88: 9608–9612.

    Article  PubMed  CAS  Google Scholar 

  • Wolkoff, A. W., 1996, Hepatocellular sinusoidal membrane organic transport and transporters, Semin. Liver Dis. 16:121–127.

    Article  PubMed  CAS  Google Scholar 

  • Wolkoff, A. W., Samuelson, A. C., Johansen, K. L., Nakata, R., Withers, D. M., and Sociak, A., 1987, Influence of Cl− on organic anion transport in short-term cultured rat hepatocytes and isolated perfused rat liver, J. Clin. Invest. 79:1259–1268.

    Article  PubMed  CAS  Google Scholar 

  • Yabuuchi, H., Tamai, I., Sai, Y., and Tsuji, A., 1998a, Possible role of anion exchanger AE2 as the intestinal monocarboxylic acid/anion antiporter, Pharmaceut. Res. 15: 409–414.

    Article  Google Scholar 

  • Yabuuchi, H. Tamai, I., Morita, K., Kouda, T., Miyamoto, K., Takeda, E. and Tsuji, A. 1998b, Hepatic sinusoidal membrane transport of anionic drugs mediated by anion transporter Npt1, J. Pharmacol. Exp. Ther. 286:139l–1396.

    Google Scholar 

  • Yamazaki, M., Suzuki, H., and Sugiyama, Y., 1996, Recent advances in carrier-mediated hepatic uptake and biliary excretion of xenobiotics, Pharmaceut. Res. 13:497–513.

    Article  CAS  Google Scholar 

  • Yamamoto, A., Sakane, T., Shibukawa, M., Hashida, M., and Sezaki, H., 1991, Absorption and metabolic characteristics of p-aminobenzoic acid and its isomer, m-aminobenzoic acid, from the rat small intestine, J. Pharmaceut. Sci. 80:1067–1071.

    Article  CAS  Google Scholar 

  • Yi, J. R., Lu, S. L., Fernandez-Checa, J. C., and Kaplowitz, N., 1995, Expression cloning of the cDNA for a polypeptide associated with rat hepatic sinusoidal reduced glutathione transport: Characteristics and comparison with the canalicular transporter, Proc. Natl. Acad. Sci. USA 92:7690–7694.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacobio-Dynamics, Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-0934, Japan

    Akira Tsuji & Ikumi Tamai

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  1. Akira Tsuji
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  2. Ikumi Tamai
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Editors and Affiliations

  1. University of Michigan, Ann Arbor, Michigan

    Gordon L. Amidon

  2. University of California, San Francisco, San Francisco, California

    Wolfgang Sadée

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© 2002 Kluwer Academic Publishers

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Tsuji, A., Tamai, I. (2002). Organic Anion Transporters. In: Amidon, G.L., Sadée, W. (eds) Membrane Transporters as Drug Targets. Pharmaceutical Biotechnology, vol 12. Springer, Boston, MA. https://doi.org/10.1007/0-306-46812-3_16

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  • DOI: https://doi.org/10.1007/0-306-46812-3_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-46094-4

  • Online ISBN: 978-0-306-46812-4

  • eBook Packages: Springer Book Archive

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