Abstract
The transport of specific molecules across lipid membranes is an essential function of all living organisms. The processes are usually mediated by specific transporters. One of the largest transporter families is the ATP-binding cassette (ABC) family. More than 40 ABC transporters have been identified in human, which are divided into 7 subfamilies (ABCA to ABCG) based on their gene structure, amino acid sequence, domain organization, and phylogenetic analysis. Of them, at least 11 ABC transporters including P-glycoprotein (P-GP/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP/ABCG2) are involved in multidrug resistance (MDR) development. These ABC transporters are expressed in various tissues such as the liver, intestine, kidney, and brain, playing important roles in absorption, distribution, and excretion of drugs. Some ABC transporters are also involved in diverse cellular processes such as maintenance of osmotic homeostasis, antigen processing, cell division, immunity, cholesterol, and lipid trafficking. Several human diseases such as cystic fibrosis, sitosterolemia, Tangier disease, intrahepatic cholestasis, and retinal degeneration are associated with mutations in corresponding transporters. This chapter will describe function and expression of several ABC transporters (such as P-GP, BCRP, and MRPs), their substrates and inhibitors, as well as their clinical significance.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Agnani D, Acharya P, Martinez E, Tran TT, Abraham F, Tobin F et al (2011) Fitting the elementary rate constants of the P-GP transporter network in the hMDR1-MDCK confluent cell monolayer using a particle swarm algorithm. PLoS One 6:e25086
Ahmed F, Arseni N, Glimm H, Hiddemann W, Buske C, Feuring-Buske M (2008) Constitutive expression of the ATP-binding cassette transporter ABCG2 enhances the growth potential of early human hematopoietic progenitors. Stem Cells 26:810–818
Akita H, Suzuki H, Sugiyama Y (2001) Sinusoidal efflux of taurocholate is enhanced in Mrp 2-deficient rat liver. Pharm Res 18:1119–1125
Akita H, Suzuki H, Sugiyama Y (2002) Sinusoidal efflux of taurocholate correlates with the hepatic expression level of Mrp3. Biochem Biophys Res Commun 299:681–687
Albrecht C, Viturro E (2007) The ABCA subfamily-Gene and protein structures, functions and associated hereditary diseases. Pflug Arch 453:581–589
Alexiou GA, Goussia A, Voulgaris S, Fotopoulos AD, Fotakopoulos G, Ntoulia A et al (2012) Prognostic significance of MRP5 immunohistochemical expression in glioblastoma. Cancer Chemother Pharmacol 69:1387–1391
Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R et al (2009) Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 323:1718–1722
Alqawi O, Bates S, Georges E (2004) Arginine482 to threonine mutation in the breast cancer resistance protein ABCG2 inhibits rhodamine 123 transport while increasing binding. Biochem J 382:711–716
Alrefai WA, Gill RK (2007) Bile Acid transporters: structure, function, regulation and pathophysiological implications. Pharm Res 24:1803–1820
Al-Shawi MK (2011) Catalytic and transport cycles of ABC exporters. Essays Biochem 50:63–83
Al-Shboul Q, Mahavadi S, Sriwai W, Grider JR, Murthy KS (2013) Differential expression of multidrug resistance protein 5 and phosphodiesterase 5 and regulation of cGMP levels in phasic and tonic smooth muscle. Am J Physiol Gastrointest Liver Physiol 305:G314–G324
Andolfo I, Russo R, Manna F, De Rosa G, Gambale A, Zouwail S et al (2016) Functional characterization of novel ABCB6 mutations and their clinical implications in familial pseudohyperkalemia. Haematologica 101:909–917
Andric SA, Kostic TS, Stojilkovic SS (2006) Contribution of multidrug resistance protein MRP5 in control of cyclic guanosine 5′-monophosphate intracellular signaling in anterior pituitary cells. Endocrinology 147:3435–3445
Anglicheau D, Pallet N, Rabant M, Marquet P, Cassinat B, Méria P et al (2006) Role of P-glycoprotein in cyclosporine cytotoxicity in the cyclosporine-sirolimus interaction. Kidney Int 70:1019–1025
Anglicheau D, Thervet E, Etienne I, Hurault De Ligny B, Le Meur Y, Touchard G et al (2004) CYP3A5 and MDR1 genetic polymorphisms and cyclosporine pharmacokinetics after renal transplantation. Clin Pharmacol Ther 75:422–433
Arana MR, Tocchetti GN, Rigalli JP, Mottino AD, Villanueva SSM (2016) Physiological and pathophysiological factors affecting the expression and activity of the drug transporter MRP2 in intestine. Impact on its function as membrane barrier. Pharmacol Res 109:32–44
Asano T, Takahashi KA, Fujioka M, Inoue S, Okamoto M, Sugioka N et al (2003) ABCB1 C3435T and G2677T/A polymorphism decreased the risk for steroid-induced osteonecrosis of the femoral head after kidney transplantation. Pharmacogenetics 13:675–682
Aittoniemi J, Fotinou C, Craig TJ, de Wet H, Proks P, Ashcroft FM (2009) SUR1: a unique ATP-binding cassette protein that functions as an ion channel regulator. Philos Trans R Soc Lond B Biol Sci 364:257–267
Baier LJ, Muller YL, Remedi MS, Traurig M, Piaggi P, Wiessner G et al (2015) ABCC8 R1420H loss-of-function variant in a Southwest American Indian community a:association with increased birth weight and double risk of type 2 diabetes. Diabetes 64:4322–4332
Bandler PE, Westlake CJ, Grant CE, Cole SPC, Deeley RG (2008) Identification of regions required for apical membrane localization of human multidrug resistance protein 2. Mol Pharmacol 74:9–19
Bardelmeijer HA, Beijnen JH, Brouwer KR, Rosing H, Nooijen WJ, Schellens JH et al (2000) Increased oral bioavailability of paclitaxel by GF120918 in mice through selective modulation of P-glycoprotein. Clin Cancer Res 6:4416–4421
Barnes KM, Dickstein B, Cutler GB Jr, Fojo T, Bates SE (1996) Steroid treatment, accumulation, and antagonism of P-glycoprotein in multidrug resistant cells. Biochemistry 35:4820–4827
Beesley J, Johnatty SE, Chen X, Spurdle AB, Peterlongo P et al (2011) No evidence for an association between the earwax-associated polymorphism in ABCC11 and breast cancer risk in Caucasian women. Breast Cancer Res Treat 126:235–239
Beis K (2015) Structural basis for the mechanism of ABC transporters. Biochem Soc Trans 43:889–893
Belinsky MG, Dawson PA, Shchaveleva I, Bain LJ, Wang R, Ling V et al (2005) Analysis of the in vivo functions of Mrp3. Mol Pharmacol 68:160–168
Belleville-Rolland T, Sassi Y, Decouture B, Dreano E, Hulot JS, Gaussem P et al (2016) MRP4 (ABCC4) as a potential pharmacologic target for cardiovascular disease. Pharmacol Res 107:381–389
Benderra Z, Faussat AM, Sayada L, Perrot JY, Tang R, Chaoui D et al (2005) MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia. Clin Cancer Res 11:7764–7772
Benzimra J, Derhy S, Rosmorduc O, Menu Y, Poupon R, Arrivé L (2013) Hepatobiliary anomalies associated with ABCB4/MDR3 deficiency in adults: a pictorial essay. Insights Imaging 4:331–338
Bera TK, Lee S, Salvatore G, Lee B, 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 7:509–516
Berger J, Forss-Petter S, Eichler FS (2014) Pathophysiology of X-linked adrenoleukodystrophy. Biochimie 98:135–142
Billat PA, Ossman T, Saint-Marcoux F, Essig M, Rerolle JP, Kamar N et al (2016) Multidrug resistance-associated protein 4 (MRP4) controls ganciclovir intracellular accumulation and contributes to ganciclovir-induced neutropenia in renal transplant patients. Pharmacol Res 111:501–508
Binkhathlan Z, Lavasanifar A (2013) P-glycoprotein inhibition as a therapeutic approach for overcoming multidrug resistance in cancer: Current status and future perspectives. Curr Cancer Drug Targets 13:326–346
Bodo A, Bakos E, Szeri F, Varadi A, Sarkadi B (2003) Differential modulation of the human liver conjugate transporters MRP2 and MRP3 by bile acids and organic anions. J Biol Chem 278:23529–23537
Bojanic DD, Tarr PT, Gale GD, Smith DJ, Bok D, Chen B et al (2010) Differential expression and function of ABCG1 and ABCG4 during development and ageing. J Lipid Res 51:169–181
Bonadia LC, de Lima Marson FA, Ribeiro JD, Paschoal IA, Pereira MC, Ribeiro AF et al (2014) CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease. Gene 540:183–190
Borst P, de Wolf C, van de Wetering K (2007) Multidrug resistance-associated proteins 3, 4, and 5 Pflugers. Arch-Eur J Physiol 453:661–673
Bouquié R, Deslandes G, Renaud C, Dailly E, Haloun A, Jolliet P (2011) Colchicine-induced rhabdomyolysis in a heart/lung transplant patient with concurrent use of cyclosporin, pravastatin, and azithromycin. J Clin Rheumatol 17:28–30
Bram E, Ifergan I, Shafran A, Berman B, Ansen G, Assaraf YG (2006) Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol 58:826–834
Bridges CC, Joshee L, van den Heuvel JJ, Russel FG, Zalups RK (2013) Glutathione status and the renal elimination of inorganic mercury in the Mrp2(−/−) mouse. PLoS One 8:e73559
Bridges CC, Joshee L, Zalups RK (2012) Placental and fetal disposition of mercuric ions in rats exposed to methylmercury: role of Mrp2. Reprod Toxicol 34:628–634
Brinar M, Cukovic-Cavka S, Bozina N, Ravic KG, Markos P, Ladic A et al (2013) MDR1 polymorphisms are associated with inflammatory bowel disease in a cohort of Croatian IBD patients. BMC Gastroenterol 13:57
Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM (1984) Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224:1121–1124
Budulac SE, Postma DS, Hiemstra PS, Kunz LI, Siedlinski M, Smit HA et al (2010) Multidrug resistance-associated protein-1(MRP1) genetic variants, MRP1 protein levels and severity of COPD. Respir Res 11:60
Budulac SE, Postma DS, Hiemstra PS, Lapperre TS, Kunz LI, Vonk JM et al (2012) Multidrug resistance-associated protein 1 and lung function decline with or without long-term corticosteroids treatment in COPD. Eur J Pharmacol 696:136–142
Burke MA, Ardehali H (2007) Mitochondrial ATP-binding cassette proteins. Transl Res 150:73–78
Calatozzolo C, Gelati M, Ciusani E, Sciacca FL, Pollo B, Cajola L et al (2005) Expression of drug resistance proteins Pgp, MRP1, MRP3, MRP5 and GST-pi in human glioma. J Neuro-Oncol 74:113–121
Canet MJ, Merrell MD, Hardwick RN, Bataille AM, Campion SN, Ferreira DW et al (2015) Altered regulation of hepatic efflux transporters disrupts acetaminophen disposition in pediatric nonalcoholic steatohepatitis. Drug Metab Dispos 43:829–835
Capparelli E, Rakhmanina N, Mirochnick M (2005) Pharmacotherapy of perinatal perinatal HIV. Semin Fetal Neonatal Med 10:161–175
Carew MW, Naranmandura H, Shukalek CB, Le XC, Leslie EM (2011) Monomethylarsenic diglutathione transport by the human multidrug resistance protein 1 (MRP1/ABCC1). Drug Metab Dispos 39:2298–2304
Carrière P, Mantha M, Champagne-Paradis S, Jumarie C (2011) Characterization of basolateral-to-apical transepithelial transport of cadmium in intestinal TC7 cell monolayers. Biometals 24:857–874
Cartwright TA, Campos CR, Cannon RE, Miller DS (2013) Mrp1 is essential for sphingolipid signaling to P-glycoprotein in mouse blood-brain and blood-spinal cord barriers. J Cereb Blood Flow Metab 33:381–388
Chell S, Kaidi A, Williams AC, Paraskeva C (2006) Mediators of PGE2 synthesis and signalling downstream of COX-2 represent potential targets for the prevention/treatment of colorectal cancer. Biochim Biophys Acta 1766:104–119
Chen ZS, Guo Y, Belinsky MG, Elena Kotova E, Kruh GD (2005) Transport of bile acids, sulfated steroids, estradiol 17-β-d-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol 67:545–557
Chen HH, Kuo MT (2010) Role of glutathione in the regulation of Cisplatin resistance in cancer chemotherapy. Met Based Drugs pii:430939
Chen ZS, Robey RW, Belinsky MG, Shchaveleva I, Ren XQ, Sugimoto Y et al (2003) Transport of methotrexate, methotrexate polyglutamates, and 17β-estradiol 17-(β-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res 63:4048–4054
Chen Z, Shi T, Zhang L, Zhu P, Deng M, Huang C et al (2016) Mammalian drug efflux transporters the ATP binding cassette (ABC) family in multidrug resistance: a review of the past decade. Cancer Lett 370:153–164
Chen JJ, Sun YL, Tiwari AK, Xiao ZJ, Sodani K, Yang DH et al (2012) PDE5 inhibitors, sildenafil and vardenafil, reverse multidrug resistance by inhibiting the efflux function of multidrug resistance protein 7 (ATP-binding Cassette C10) transporter. Cancer Sci 103:1531–1537
Chen ZS, Tiwari AK (2011) Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases. FEBS J 278:3226–3245
Chen Y, Vasilenko A, Song X, Valanejad L, Verma R, You S et al (2015) Estrogen and estrogen receptor-α-mediated transrepression of bile salt export pump. Mol Endocrinol 29:613–626
Cheng X, Maher J, Chen C, Klaassen CD (2005) Tissue distribution and ontogeny of mouse organic anion transporting polypeptides (Oatps). Drug Metab Dispos 33:1062–1073
Chiaw PK, Eckford PDW, Bear CE (2011) Insights into the mechanisms underlying CFTR channel activity, the molecular basis for cystic fibrosis and strategies for therapy. Essays Biochem 50:233–248
Claude C, Mougenot N, Bechaux J, Hadri L, Brockschnieder D, Clergue M et al (2015) Inhalable delivery of AAV-based MRP4/ABCC4 silencing RNA prevents monocrotaline-induced pulmonary hypertension. Mol Ther Methods Clin Dev 2:14065
Coelho D, Kim JC, Miousse IR, Fung S, du Moulin M, Buers I et al (2012) Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. Nat Genet 44:1152–1155
Cohen O, Locketz G, Hershko AY, Gorshtein A, Levy Y (2015) Colchicine- clarithromycin-induced rhabdomyolysis in Familial Mediterranean Fever patients under treatment for Helicobacter pylori. Rheumatol Int 35:1937–1941
Cole SP (2014) Multidrug resistance protein 1(MRP1,ABCC1), a “multitasking” ATP-binding cassette (ABC) transporter. J Biol Chem 289:30880–30888
Copsel S, Bruzzone A, May M, Beyrath J, Wargon V, Cany J et al (2014) Multidrug resistance protein 4/ ATP binding cassette transporter 4: a new potential therapeutic target for acute myeloid leukemia. Oncotarget 5:9308–9321
Copsel S, Garcia C, Diez F, Vermeulem M, Baldi A, Bianciotti LG et al (2011) Multidrug resistance protein 4 (MRP4/ABCC4) regulates cAMP cellular levels and controls human leukemia cell proliferation and differentiation. J Biol Chem 286:6979–6988
Cuperus FJ, Claudel T, Gautherot J, Halilbasic E, Trauner M (2014) The role of canalicular ABC transporters in cholestasis. Drug Metab Dispos 42:546–560
Cusatis G, Gregorc V, Li J, Spreafico A, Ingersoll RG, Verweij J et al (2006) Pharmacogenetics of ABCG2 and adverse reactions to gefi tinib. J Natl Cancer Inst 98:1739–1742
Dahan A, Amidon GL (2009) Segmental dependent transport of low permeability compounds along the small intestine due to p-glycoprotein: the role of efflux transport in the oral absorption of BCS class III drugs. Mol Pharm 6:19–28
Dahan A, Sabit H, Amidon GL (2009) Multiple efflux pumps are involved in the transepithelial transport of colchicine: combined effect of P-glycoprotein and multidrug resistance-associated protein 2 leads to decreased intestinal absorption throughout the entire small intestine. Drug Metabo Dispos 37:2028–2036
Damiani D, Tiribelli M, Calistri E, Geromin A, Chiarvesio A et al (2006) The prognostic value of P-glycoprotein (ABCB) and breast cancer resistance protein (ABCG2) in adults with de novo acute myeloid leukemia with normal karyotype. Haematologica 91:825–828
Damiani D, Tiribelli M, Geromin A, Michelutti A, Cavallin M, Sperotto A et al (2015) ABCG2 overexpression in patients with acute myeloid leukemia: impact on stem cell transplantation outcome. Am J Hematol 90:784–789
Dantzig AH, Shepard RL, Cao J, Law KL, Ehlhardt WJ, Baughman TM et al (1996) Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res 56:4171–4179
Dantzig AH, Shepard RL, Law KL, Tabas L, Pratt S, Gillespie JS et al (1999) Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities. J Pharmacol Exp Ther 290:854–862
Dazert P, Meissner K, Vogelgesang S, Heydrich B, Eckel L, Böhm M et al (2003) Expression and localization of the multidrug resistance protein 5 (MR5/ABCC5), a cellular export pump for cyclic nucleotides, in human heart. Am J Pathol 163:1567–1577
de Vries NA, Zhao J, Kroon E, Buckle T, Beijnen JH, van Tellingen O (2007) P-glycoprotein and breast cancer resistance protein: two dominant transporters working together in limiting the brain penetration of topotecan. Clin Cancer Res 13:6440–6449
Dean M, Rzhetsky A, Allikmets R (2001) The human ATP-binding cassette(ABC) transporter superfamily. Genome Res 11:1156–1166
De Lannoy IA, Koren G, Klein J, Charuk J, Silverman M (1992) Cyclosporin and quinidine inhibition of renal digoxin excretion: evidence for luminal secretion of digoxin. Am J Phys 263(4 Pt 2):F613–F622
de Jong FA, Scott-Horton TJ, Kroetz DL, McLeod HL, Friberg LE, Mathijssen RH et al (2007) Irinotecan-induced diarrhea: functional significance of the polymorphic ABCC2 transporter protein. Clin Pharmacol Ther 81:42–49
Decouture B, Dreano E, Belleville-Rolland T, Kuci O, Dizier B, Amine Bazaa A et al (2015) Impaired platelet activation and cAMP homeostasis in MRP4-deficient Mice. Blood 126:1823–1830
del Moral RG, Andujar M, Ramírez C, Gómez-Morales M, Masseroli M, Aguilar M et al (1997) Chronic cyclosporin A nephrotoxicity, P-glycoprotein overexpression, and relationships with intrarenal angiotensin II deposits. Am J Pathol 151:1705–1714
Deme JC, Hancock MA, Xia X, Shintre CA, Plesa M, Kim JC et al (2014) Purification and interaction analyses of two human lysosomal vitamin B12 transporters: LMBD1 and ABCD4. Mol Membr Biol 31:250–261
Diamanti AP, Rosado M, Germano V, Scarsella M, Giorda E, Podestà E et al (2011) Reversion of resistance to immunosuppressive agents in three patients with psoriatic arthritis by cyclosporine A: modulation of P-glycoprotein function. Clin Immunol 138:9–13
Dickens D, Owen A, Alfirevic A, Pirmohamed M (2013) ABCB1 single nucleotide polymorphisms(1236C>T, 2677G>T, and 3435C>T) do not affect transport activity of human P-glycoprotein. Pharmacogenet Genomics 23:314–323
Dietrich CG, Vehr AK, Martin IV, Gaβer N, Rath T, Roeb E et al (2011) Downregulation of breast cancer resistance protein in colon adenomas reduces cellular xenobiotic resistance and leads to accumulation of a food-derived carcinogen. Int J Cancer 129:546–552
Do TM, Noel-Hudson MS, Ribes S, Besengez C, Smirnova M, Cisternino S et al (2012) ABCG2- and ABCG4-mediated efflux of amyloid-β peptide (1-40) at the mouse blood-brain barrier. J Alzheimers Dis 30:155–166
Drach J, Gsur A, Hamilton G, Zhao S, Angerler J, Fiegl M et al (1996) Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4, and interferon-gamma in normal human T lymphocytes. Blood 88:1747–1175
Drenberg CD, Hu S, Li L, Buelow DR, Orwick SJ, Gibson AA et al (2016) ABCC4 is a determinant of cytarabine-induced cytotoxicity and myelosuppression. Clin Transl Sci 9:51–59
Drescher S, Schaeffeler E, Hitzl M, Hofmann U, Schwab M, Brinkmann U et al (2002) MDR1 gene polymorphisms and disposition of the P-glycoprotein substrate fexofenadine. Br J Clin Pharmacol 53:526–534
Drozdzik M, Gröer C, Penski J, Lapczuk J, Ostrowski M, Lai Y et al (2014) Protein abundance of clinically relevant multidrug transporters along the entire length of the human intestine. Mol Pharm 11:3547–3555
Dzierlenga AL, Clarke JD, Hargraves TL, Ainslie GR, Vanderah TW, Mary F, Paine MF et al (2015) Mechanistic basis of altered morphine disposition in nonalcoholic steatohepatitis. J Pharmacol Exp Ther 352:462–470
Eckford PD, Sharom FJ (2009) ABC efflux pump-based resistance to chemotherapy drugs. Chem Rev 109:2989–3011
Emadi A, Gore SD (2010) Arsenic trioxide- An old drug rediscovered. Blood Rev 24:191–199
Engelen M, Kemp S, Poll-The BT (2014) X-linked adrenoleukodystrophy: pathogenesis and treatment. Curr Neurol Neurosci Rep 14:486
Engström K, Ameer S, Bernaudat L, Drasch G, Baeuml J, Skerfving S et al (2013) Polymorphisms in genes encoding potential mercury transporters and urine mercury concentrations in populations exposed to mercury vapor from gold mining. Environ Health Perspect 121:85–91
Ernest S, Bello-Reuss E (1999) Secretion of platelet-activating factor is mediated by MDR1 P-glycoprotein in cultured human mesangial cells. J Am Soc Nephrol 10:2306–2313
Eytan GD, Regev R, Assaraf YG (1996) Functional reconstitution of P-glycoprotein reveals an apparent near stoichiometric drug transport to ATP hydrolysis. J Biol Chem 271:3172–3178
Fan Y, Liu XD (2018) Alterations in expression and function of abc family transporters at blood-brain barrier under liver failure and their clinical significances. Pharmaceutics 10:102
Fanen P, Wohlhuter-Haddad A, Hinzpeter A (2014) Genetics of cystic fibrosis: CFTR mutation classifications toward genotype-based CF therapies. Int J Biochem Cell Biol 52:94–102
Fardel O, Jigorel E, Le Vee M, Payen L (2005) Physiological, pharmacological and clinical features of the multidrug resistance protein 2. Biomed Pharmacother 59:104–114
Fatima S, Zhou S, Sorrentino BP (2012) Abcg2 expression marks tissue-specific stem cells in multiple organs in a mouse progeny tracking model. Stem Cells 30:210–221
Fernández-Barrena MG, Monte MJ, Latasa MU, Uriarte I, Vicente E, Haisul CY, HCY C et al (2012) Lack of Abcc3 expression impairs bile-acid induced liver growth and delays hepatic regeneration after partial hepatectomy in mice. J Hepatol 56:367–373
Ferslew BC, Johnston CK, Tsakalozou E, Bridges AS, Paine MF et al (2015) Altered morphine glucuronide and bile acid disposition in patients with non-alcoholic steatohepatitis. Clin Pharmacol Ther 97:419–427
Flanagan SE, Clauin S, Bellanné-Chantelot C, de Lonlay P, Harries LW, Gloyn AL et al (2009) Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat 30:170–180
Fox E, Widemann BC, Pastakia D, Chen CC, Yang SX, Cole D et al (2015) Pharmacokinetic and pharmacodynamic study of tariquidar (XR9576), a P-glycoprotein inhibitor, in combination with doxorubicin, vinorelbine, or docetaxel in children and adolescents with refractory solid tumors. Cancer Chemother Pharmacol 76:1273–1283
Fellay J, Marzolini C, Meaden ER, Back DJ, Buclin T, Chave JP et al (2002) Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 359:30–36
Filipits M, Pohl G, Rudas M, Dietze O, Lax S, Grill R et al (2005) Clinical role of multidrug resistance protein 1 expression in chemotherapy resistance in early-stage breast cancer: the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 23:1161–1168
Frank MH, Denton MD, Alexander SI, Khoury SJ, Sayegh MH, Briscoe DM (2001) Specific MDR1 P-glycoprotein blockade inhibits human alloimmune T cell activation in vitro. J Immunol 166:2451–2459
Fricker G, Drewe J, Huwyler J, Gutmann H, Beglinger C (1996) Relevance of p-glycoprotein for the enteral absorption of cyclosporin A: in vitro-in vivo correlation. Br J Pharmacol 118:1841–1847
Fu Y, Hsiao JH, Paxinos G, Halliday GM, Kim WS (2015) ABCA5 regulates amyloid-β peptide production and is associated with Alzheimer’s disease neuropathology. J Alzheimers Dis 43:857–869
Fukuda Y, Cheong PL, Lynch J, Brighton C, Frase S, Kargas V et al (2016) The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6. Nat Commun 7:12353
Fukuda Y, Takenaka K, Sparreboom A, Cheepala SB, Wu CP, Sean Ekins S et al (2013) Human immunodeficiency virus protease inhibitors interact with ATP binding cassette transporter 4/multidrug resistance protein 4: a basis for unanticipated enhanced cytotoxicity. Mol Pharmacol 84:361–371
Fung KL, Gottesman MM (2009) A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function. Biochim Biophys Acta 1794:860–871
Gadsby DC, Vergani P, Csanady L (2006) The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 440:477–483
Gazzaniga P, Gradilone A, Petracca A, Nicolazzo C, C Raimondi C, Iacovelli R et al (2010) Molecular markers in circulating tumour cells from metastatic colorectal cancer patients. J Cel Mol Med 14:2073–2077
George AM, Jones PM (2012) Perspectives on the structure-function of ABC transporters: the Switch and Constant Contact models. Prog Biophys Mol Biol 109:95–107
Gerloff T, Schaefer M, Johne A, Oselin K, Meisel C, Cascorbi I et al (2002) MDR1 genotypes do not influence the absorption of a single oral dose of 1 mg digoxin inhealthy white males. Br J Clin Pharmacol 54:610–616
Geyer J, Gavrilova O, Petzinger E (2009) Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. J Vet Pharmacol Ther 32:87–96
Ghafouri H, Ghaderi B, Amini S, Nikkhoo B, Abdi M, Hoseini A (2016) Association of ABCB1 and ABCG2 single nucleotide polymorphisms with clinical findings and response to chemotherapy treatments in Kurdish patients with breast cancer. Tumor Biol 37:7901–7906
Glover JA, Hughes CM, Cantwell MM, Murray LJ (2011) A systematic review to establish the frequency of cyclooxygenase-2 expression in normal breast epithelium, ductal carcinoma in situ, microinvasive carcinoma of the breast and invasive breast cancer. Br J Cancer 105:13–17
Gomes T, Mamdani MM, Juurlink DN (2009) Macrolide-induced digoxin toxicity: a population-based study. Clin Pharmacol Ther 86:383–386
Grant CE, Gao M, DeGorter MK, Cole SP, Deeley RG (2008) Structural determinants of substrate specificity differences between human multidrug resistance protein (MRP) 1 (ABCC1) and MRP3(ABCC3). Drug Metab Dispos 36:2571–2581
Greenhough A, Smartt HJM, Moore AE, Roberts HR, Williams AC, Paraskeva C et al (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcino- genesis 30:377–386
Guo Y, Kock K, Ritter CA, Chen ZS, Grube M, Jedlitschky G et al (2009) Expression of ABCC-type nucleotide exporters in blasts of adult acute myeloid leukemia: relation to long-term survival. Clin Cancer Res 15:1762–1769
Guo Y, Kotova E, Chen ZS, Lee K, Hopper-Borge E, Belinsky MG et al (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
Gupta N, Martin PM, Miyauchi S, Ananth S, Herdman AV, Martindale RG et al (2006) Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer. Biochem Biophys Res Commun 343:571–577
Gupta A, Zhang Y, Unadkat JD, Mao Q (2004) HIV protease inhibitors are nhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther 310:334–341
Haber M, Smith J, Bordow SB, Flemming C, Cohn SL, London WB et al (2006) Association of high-level MRP1 expression with poor clinical outcome in a large prospective study of primary neuroblastoma. J Clin Oncol 24:1546–1553
Haghverdizadeh P, Haerian MS, Haghverdizadeh P, Haerian BS (2014) ABCC8 genetic variants and risk of diabetes mellitus. Gene 545:198–204
Halon A, Materna V, Donizy P, Matkowski R, Rabczynski J, Lage H, Surowiak P (2013) MRP2 (ABCC2, cMOAT) expression in nuclear envelope of primary fallopian tube cancer cells is a new unfavorable prognostic factor. Arch Gynecol Obstet 287:563–570
Hara Y, Sassi Y, Guibert C, Gambaryan N, Dorfmüller P, Eddahibi S et al (2011) Inhibition of MRP4 prevents and reverses pulmonary hypertension in mice. J Clin Invest 121:2888–2897
Harrington AM, Castro J, Young RL, Kurtz CB, Silos-Santiago I, Nguyen NQ et al (2014) Distinct alterations in the guanylate cyclase-C (GC-C)/cyclic GMP (cGMP) pathway are evident across different subtypes of irritable bowel syndrome (IBS) patients. Gastroenterology 146:S-537
Hasegawa Y, Kishimoto S, Takahashi H, Inotsume N, Takeuchi Y, Fukushima S (2009) Altered expression of MRP2, MRP3 and UGT2B1 in the liver affects the disposition of morphine and its glucuronide conjugate in a rat model of cholestasis. J Pharm Pharmacol 61:1205–1210
Hattori H, Suminoe A, Wada M, Koga Y, Kohno K, Okamura J et al (2007) Regulatory polymorphisms of multidrug resistance 1(MDR1) gene are associated with the development of childhood acute lymphoblastic leukemia. Leuk Res 31:1633–1640
Hawwa AF, McKiernan PJ, Shields M, Millership JS, Collier PS, McElnay JC (2009) Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant. Br J Clin Pharmacol 68:413–421
Hazard SE, Patel SB (2007) Sterolins ABCG5 and ABCG8: regulators of whole body dietary sterols. Pflugers Arch 453:745–752
Hedman A, Angelin B, Arvidsson A, Dahlqvist R, Nilsson B (1990) Interactions in the renal and biliary elimination of digoxin: stereoselective difference between quinine and quinidine. Clin Pharmacol Ther 47:20–26
Henderson MJ, Haber M, Porro A, Munoz MA, Iraci N, Xue C et al (2011) ABCC multidrug transporters in childhood neuroblastoma: clinical and biological effects independent of cytotoxic drug efflux. J Natl Cancer Inst 103:1236–1251
Henmi K, Yoshida M, Yoshikawa N, Hirano T (2008) P-glycoprotein functions in peripheral-blood CD4+ cells of patients with systemic lupus erythematosus. Biol Pharm Bull 31:873–878
Higgins CF, Linton KJ (2004) The ATP switch model for ABC transporters. Nat Struct Mol Bio 11:918–926
Hinz A, Tampé R (2012) ABC Transporters and immunity: mechanism of self-defense. Biochemistry 51:4981–4989
Hirohashi T, Suzuki H, Takikawa H, Sugiyama Y (2000) ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3(Mrp3). J Biol Chem 275:2905–2910
Hitzl M, Drescher S, van der Kuip H, Schäffeler E, Fischer J, Schwab M et al (2001) The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells. Pharmacogenetics 11:293–298
Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmöller J, Johne A et al (2000) Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A 97:3473–3478
Honjo Y, Hrycyna CA, Yan QW, WY M-P’r, Robey RW, van de Laar A et al (2001) Acquired Mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res 61:6635–6639
Hopper-Borge EA, Churchill T, Paulose C, Nicolas E, Jacobs JD, Ngo O et al (2011) Contribution of Abcc10 (Mrp7) to in vivo paclitaxel resistance as assessed in Abcc10(−/−) mice. Cancer Res 71:3649–3657
Hosomi A, Nakanishi T, Fujita T, Tamai I (2012) Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2. PLoS One 7:e30456
Hu LL, Wang XX, Chen X, Chang J, Li C, Zhang Y et al (2007) BCRP gene polymorphisms are associated with susceptibility and survival of diffuse large B-cell lymphoma. Carcinogenesis 28:1740–1744
Huls M, Russel FGM, Masereeuw R (2009) The role of ATP binding cassette transporters in tissue defense and organ regeneration. J Pharmacol Exp Ther 328:3–9
Huisman MT, Smit JW, Wiltshire HR, Hoetelmans RM, Beijnen JH, Schinkel AH (2001) P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir. Mol Pharmacol 59:806–813
Huisman MT, Smit JW, Wiltshire HR, Beijnen JH, Schinkel AH (2003) Assessing safety and efficacy of directed P-glycoprotein inhibition to improve the pharmacokinetic properties of saquinavir coadministered with ritonavir. J Pharmacol Exp Ther 304:596–602
Huynh T, Norris MD, Haber M, Henderson MJ (2012) ABCC4/MRP4: MYCN-regulated transporter and potential therapeutic target in neuroblastoma. Front Oncol 2:178
Ichida K, Matsuo H, Takada T, Nakayama A, Murakami K, Shimizu T et al (2012) Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun 3:764
Imaoka T, Kusuhara H, Adachi M, Schuetz JD, Takeuchi K, Sugiyama Y (2007) Functional involvement of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the renal elimination of the antiviral drugs adefovir and tenofovir. Mol Pharmacol 71:619–627
Ishizuka H, Konno K, Shiina T, Naganuma H, Nishimura K, Ito K, Suzuki H, Sugiyama Y (1999) Species differences in the transport activity for organic anions across the bile canalicular membrane. J Pharmacol Exp Ther 290:1324–1330
Ito S, Ieiri I, Tanabe M, Suzuki A, Higuchi S, Otsubo K (2001a) Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects. Pharmacogenetics 11:175–184
Ito K, Olsen SL, Qiu W, Deeley RG, Cole SP (2001b) Mutation of a single conserved tryptophan in multidrug resistance protein 1 (MRP1/ABCC1) results in loss of drug resistance and selective loss of organic anion transport. J Biol Chem 276:15616–15624
Ito S, Iwaki S, Koike K, Yuda Y, Nagasaki A, Ohkawa R et al (2013) Increased plasma sphingosine-1-phosphate in obese individuals and its capacity to increase the expression of plasminogen activator inhibitor-1 in adipocytes. Coron Artery Dis 24:642–650
Jamroziak K, Młynarski W, Balcerczak E, Mistygacz M, Trelinska J, Mirowski M et al (2004) Functional C3435T polymorphism of MDR1 gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic leukemia. Eur J Haematol 72:314–321
Jansen RS, Mahakena S, de Haas M, Borst P, van de Wetering K (2015) ATP-binding cassette subfamily C member 5 (ABCC5) functions as an efflux transporter of glutamate conjugates and analogs. J Biol Chem 290:30429–30440
Jedlitschky G, Burchell B, Keppler D (2000) The Multidrug resistance protein 5 functions as an atp-dependent export pump for cyclic nucleotides. J Biol Chem 275:30069–30074
Jedlitschky G, Cattaneo M, Lubenow LE, Rosskopf D, Lecchi A, Artoni A et al (2010) Role of MRP4 (ABCC4) in platelet adenine nucleotide-storage: evidence from patients with delta-storage pool deficiencies. Am J Pathol 176:1097–1103
Jedlitschky G, Tirschmann K, Lubenow LE, Nieuwenhuis HK, Akkerman JW, Greinacher A et al (2004) The nucleotide transporter MRP4 (ABCC4) is highly expressed in human platelets and present in dense granules, indicating a role in mediator storage. Blood 104:3603–3610
Jin F, Zhao L, Zhao HY, Guo SG, Feng J, Jiang XB et al (2008) Comparison between cells and cancer stem-like cells isolated from glioblastoma and astrocytoma on expression of anti-apoptotic and multidrug resistance-associated protein genes. Neuroscience 154:541–550
Jing X, Liu X, Wen T, Xie S, Yao D, Liu X et al (2010) Combined effect of epileptic seizure and drug induction resulted in overexpression of P-glycoprotein in brain of kindled rats. Brit J Pharmacol 159:1511–1522
Johne A, Köpke K, Gerloff T, Mai I, Rietbrock S, Meisel C et al (2002) Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene. Clin Pharmacol Ther 72:584–594
Johnson DR, Finch RA, Lin ZP, Zeiss CJ, Sartorelli AC (2001) The pharmacological phenotype of combined multidrug-resistance mdr1a/1b- and mrp1-deficient mice. Cancer Res 61:1469–1476
Jones DC, Duvauchelle C, Ikegami A, Olsen CM, Lau SS, de la Torre R et al (2005) Serotonergic neurotoxic metabolites of ecstasy identified in rat brain. J Pharmacol Exp Ther 313:422–431
Jonker JW, Buitelaar M, Wagenaar E, Van Der Valk MA, Scheffer GL, Scheper RJ et al (2002) The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci U S A 99:15649–15654
Jonker JW, Smit JW, Brinkhuis RF, Maliepaard M, Beijnen JH et al (2000) Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst 92:1651–1656
Kamisako T, Ogawa H (2005) Alteration of the expression of adenosine triphosphate-binding cassette transporters associated with bile acid and cholesterol transport in the rat liver and intestine during cholestasis. J Gastroenterol Hepatol 20:1429–1434
Kathawala RJ, Sodani K, Chen K, Patel A, Abuznait AH, Anreddy N, Sun YL et al (2014) Masitinib antagonizes ATP-binding cassette subfamily C member 10-mediated paclitaxel resistance: a preclinical study. Mol Cancer Ther 13:714–723
Kathawala RJ, Wei L, Anreddy N, Anreddy N, Chen K, Patel A et al (2015) The small molecule tyrosine kinase inhibitor NVP-BHG712 antagonizes ABCC10-mediated paclitaxel resistance: a preclinical and pharmacokinetic study. Oncotarget 6:510–521
Kawaguchi K, Okamoto T, Morita M, Imanaka T (2016) Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1. Sci Rep 6:30183
Kemp S, Berger J, Aubourg P (2012) X-linked adrenoleukodystrophy: Clinical, metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta 1822:1465–1474
Kim YH, Ishii G, Goto K, Ota S, Kubota K, al MY (2009a) Expression of breast cancer resistance protein is associated with a poor clinical outcome in patients with small-cell lung cancer. Lung Cancer 65:105–111
Kim DH, Sriharsha L, Xu W, Kamel-Reid S, Liu X, Siminovitch K et al (2009b) Clinical relevance of a pharmacogenetic approach using multiple candidate genes to predict response and resistance to imatinib therapy in chronic myeloid leukemia. Clin Cancer Res 15:4750–4758
Kim JC, Lee NC, Hwu PW, Chien YH, Fahiminiya S, Majewski J et al (2012) Late onset of symptoms in an atypical patient with the cblJ inborn error of vitamin B12 metabolism: diagnosis and novel mutation revealed by exome sequencing. Mol Genet Metab 107:664–668
Kitamura Y, Hirouchi M, Kusuhara H, Schuetz JD, Sugiyama Y (2008) Increasing systemic exposure of methotrexate by active efflux mediated by multidrug resistance-associated protein 3 (Mrp3/Abcc3). J Pharmacol Exp Ther 327:465–473
Kitamura Y, Kusuhara H, Sugiyama Y (2010) Basolateral efflux mediated by multidrug resistance-associated protein 3(Mrp3/Abcc3) facilitates intestinal absorption of folates in mouse. Pharm Res 27:665–672
Kobuchi H, Moriya K, Ogino T, Fujita H, Inoue K, Shuin T et al (2012) Mitochondrial localization of ABC transporter ABCG2 and Its function in 5-aminolevulinic acid-mediated protoporphyrin IX accumulation. PLoS One 7:e50082
Kochel TJ, Olga G, Goloubeva QG, Fulton AM (2016) Upregulation of cyclooxygenase-2 /prostaglandin E2 (COX-2/PGE2) pathway member multiple drug resistance-associated protein 4 (MRP4) and downregulation of prostaglandin transporter (PGT) and 15-prostaglandin dehydrogenase (15-PGDH) in triple-negative breast cancer. Breast Cancer (Auckl) 10:61–70
Kochel TJ, Fulton AM (2015) Multiple drug resistance-associated protein 4 (MRP4), prostaglandin transporter (PGT), and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) as determinants of PGE2 levels in cancer. Prostaglandins Other Lipid Mediat 116–117:99–103
Kohler JJ, Hosseini SH, Green E, Abuin A, Ludaway T, Russ R et al (2011) Tenofovir renal proximal tubular toxicity is regulated by OAT1 and MRP4 transporters. Lab Investig 91:852–858
Komoto C, Nakamura T, Sakaeda T, Kroetz DL, Yamada T, Omatsu H et al (2006) MDR1 haplotype frequencies in Japanese and Caucasian, and in Japanese patients with colorectal cancer and esophageal cancer. Drug Metab Pharmacokinet 21:126–132
Konig J, Rost D, Cui Y, Keppler D (1999) Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane. Hepatology 29:1156–1163
Koo DH, Ryu MH, Ryoo BY, Beck MY, Na YS, Shin JG et al (2015) Association of ABCG2 polymorphism with clinical efficacy of imatinib in patients with gastrointestinal stromal tumor. Cancer Chemother Pharmacol 75:173–182
Kooij G, Backer R, Koning JJ, Reijerkerk A, van Horssen J, van der Pol SM et al (2009) P-glycoprotein acts as an immunomodulator during neuroinflammation. PLoS One 4:e8212
Kooij G, van Horssen J, de Lange EC, Reijerkerk A, van der Pol SM, van Het Hof B et al (2010) T lymphocytes impair P-glycoprotein function during neuroinflammation. J Autoimmun 34:416–425
Kool M, de Haas M, Scheffer GL, Scheper RJ, van Eijk MJ, Juijn JA et al (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
Korenaga Y, Naito K, Okayama N, Hirata H, Suehiro Y, Hamanaka Y et al (2005) Association of the BCRP C421A polymorphism with nonpapillary renal cell carcinoma. Int J Cancer 117:431–434
Korita PV, Wakai T, Shirai Y, Matsuda Y, Sakata J, Takamura M et al (2010) Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma. Oncol Rep 23:965–972
Koziolek MJ, Riess R, Geiger H, Thévenod F, Hauser IA (2001) Expression of multidrug resistance P-glycoprotein in kidney allografts from cyclosporine A-treated patients. Kidney Int 60:156–166
Krishnamurthy P, Ross DD, Nakanishi T, Bailey-Dell K, Zhou S, Mercer KE et al (2004) The Stem Cell Marker Bcrp/ABCG2 Enhances Hypoxic Cell Survival through Interactions with Heme. J Bio Chem 279:24218–24225
Krishnamurthy P, Schuetz JD (2011) The role of ABCG2 and ABCB6 in porphyrin metabolism and cell survival. Curr Pharm Biotechnol 12:647–655
Krishnamurthy P, Schwab M, Takenaka K, Nachagari D, Morgan J, Leslie M et al (2008) Transporter-mediated protection against thiopurine-induced hematopoietic toxicity. Cancer Res 68:4983–4989
Kubitz R, Dröge C, Stindt J, Weissenberger K, Häussinger D (2012) The bile salt export pump (BSEP) in health and disease. Clin Res Hepatol Gastroenterol 36:536–553
Kusuhara H, Sugiyama Y (2007) ATP-binding cassette, subfamily G (ABCG family). Pflugers Arch 453:735–744
Kuan CT, Wakiya K, Herndon JE II, Lipp ES, Pegram CN, Riggins GJ et al (2010) MRP3: a molecular target for human glioblastoma multiforme immunotherapy. BMC Cancer 10:468
Kurzawski M, Bartnicka L, Florczak M, Górnik W, Droździk M (2007) Impact of ABCB1 (MDR1) gene polymorphism and P-glycoprotein inhibitors on digoxin serum concentration in congestive heart failure patients. Pharmacol Rep 59:107–111
Lang T, Justenhoven C, Winter S, Baisch C, Hamann U, Harth V et al (2011) The earwax- associated SNP c.538G>A (G180R) in ABCC11 is not associated with breast cancer risk in Europeans. Breast Cancer Res Treat 129:993–999
Lee J, Wang R, Yang Y, Lu X, Zhang X, Wang L, Lou Y (2015) The effect of ABCB1 C3435T polymorphism on cyclosporine dose requirements in kidney transplant recipients: a meta-analysis. Basic Clin Pharmacol Toxicol 117:117–125
Lee JS, Jung ID, Lee CM, Noh KT, Park JW, Son KH et al (2011) Venlafaxine inhibits the development and differentiation of dendritic cells through the regulation of P-glycoprotein. Int Immunopharmacol 11:1348–1357
Lemos C, Giovannetti E, Zucali PA, Assaraf YG, Scheffer GL, van der Straaten T (2011) Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients. Pharmacogenomics 12:159–170
Leslie EM (2012) Arsenic-glutathione conjugate transport by the human multidrug resistance proteins (MRPs/ABCCs). J Inorg Biochem 108:141–149
Leslie EM, Deeley RG, Cole SPC (2005) Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 204:216–237
Li H, Karl T, Garner B (2015) Understanding the function of ABCA7 in Alzheimer’s disease. Biochem Soc Trans 43:920–923
Li C, Krishnamurthy PC, Penmatsa H, Marrs KL, Wang XQ, Zaccolo M et al (2007) Spatiotemporal coupling of cAMP transporter to CFTR chloride channel function in the gut epithelia. Cell 131:940–951
Li J, Li ZN, Yu LC, Bao QL, Wu JR, Shi SB et al (2010) Association of expression of MRP1, BCRP, LRP and ERCC1 with outcome of patients with locally advanced non-small cell lung cancer who received neoadjuvant chemotherapy. Lung Cancer 69:116–122
Li N, Zhang Y, Hua F, Lai Y (2009) Absolute difference of hepatobiliary transporter multidrug resistance-associated protein (MRP2/Mrp2) in liver tissues and isolated hepatocytes from rat, dog, monkey, and human. Drug Metab Dispos 37:66–73
Liang SC, Yang CY, Tseng JY, Wang HL, Tung CY, Liu HW et al (2015) ABCG2 localizes to the nucleus and modulates cdh1 expression in lung cancer cells. Neoplasia 17:265–278
Lickteig AJ, Fisher CD, Augustine LM, Aleksunes LM, Besselsen DG, Slitt AL, Manautou JE et al (2007) Efflux transporter expression and acetaminophen metabolite excretion are altered in rodent models of nonalcoholic fatty liver disease. Drug Metab Dispos 35:1970–1978
Lin JH, Yamazaki M (2003) Clinical relevance of P-glycoprotein in drug therapy. Drug Metab Rev 35:417–454
Lindberg-Freijs A, Karlsson MO (1994) Dose dependent absorption and linear disposition of cyclosporine A in rat. Biopharm Drug Dispos 15:75–86
Liu H, Zhang D, Xu X, Liu X, Wang G, Xie L et al (2007) Attenuated function and expression of P-glycoprotein at blood-brain barrier and increased brain distribution of phenobarbital in streptozotocin-induced diabetic mice. Euro J Pharmacol 561:226–232
Liu L, Liu XD (2014) Alterations in function and expression of ABC transporters at blood-brain barrier under diabetes and the clinical significances. Front Pharmacol 5:273
Liu XD, Zhang L, Xie L (2003) Effect of P-glycoprotein inhibitors erythromycin and cyclosporine A on brain pharmacokinetics of nimodipine in rats. Eur J Drug Metab Pharmacokinet 28:309–313
Liu XD, Pan GY, Xie L, Hou YY, Lan W, Su Q et al (2002) Cyclosporin A enhanced protection of nimodipine against brain damage induced by hypoxia-ischemia in mice and rats. Acta Pharmacol Sin 23:225–229
Liu Y, Yin Y, Sheng Q, Lu X, Wang F, Lin Z et al (2014) Association of ABCC2 224C.T polymorphism with High-dose methotrexate plasma concentrations and toxicities in childhood acute lymphoblastic leukemia. PLoS One 9:e82681
Llaudó I, Colom H, Giménez-Bonafé P, Torras J, Caldés A, Sarrias M et al (2013) Do drug transporter (ABCB1) SNPs and P-glycoprotein function influence cyclosporine and macrolides exposure in renal transplant patients? Results of the pharmacogenomics substudy within the symphony study. Transpl Int 26:177–186
Loging WT, Lal A, Siu IM, Loney TL, Carol J, Wikstrand CJ et al (2000) Identifying potential tumor markers and antigens by database mining and rapid expression screening. Genome Res 10:1393–1402
Loh PT, Lou HX, Zhao Y, Chin YM, Vathsala A (2008) Significant impact of gene polymorphisms on tacrolimus but not cyclosporine dosing in Asian renal transplant recipients. Transplant Proc 40:1690–1695
Low SK, Fukunaga K, Takahashi A, Matsuda K, Hongo F et al (2016) Association study of a functional variant on ABCG2 gene with sunitinib-induced severe adverse drug reaction. PLoS One 11:e0148177
Lynch J, Fukuda Y, Krishnamurthy P, Du G, Schuetz JD (2009) Cell survival under stress is enhanced by a mitochondrial ATP-binding cassette transporter that regulates hemoproteins. Cancer Res 69:5560–5567
Maciejczyk A, Jagoda E, Wysocka T, Matkowski R, Györffy B, Lage H et al (2012) ABCC2 (MRP2, cMOAT) localized in the nuclear envelope of breast carcinoma cells correlates with poor clinical outcome. Pathol Oncol Res 18:331–342
Maeno K, Nakajima A, Conseil G, Rothnie A, Deeley RG, Cole SPC (2009) Molecular basis for reduced estrone sulfate transport and altered modulator sensitivity of transmembrane helix (TM) 6 and TM17 mutants of multidrug resistance protein 1 (ABCC1). Drug Metabo Dispo 37:1411–1420
Malingré MM, Beijnen JH, Rosing H, Koopman FJ, Jewell RC, Paul EM et al (2001) Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients. Br J Cancer 84:42–47
Mao Q, Unadkat JD (2014) Role of the breast cancer resistance protein (BCRP/ABCG2) in drug transport—an update. AAPS J 17:65–82
Marzolini C, Rudin C, Decosterd LA, Telenti A, Schreyer A, Biollaz J et al (2002) Transplacental passage of protease inhibitors at delivery. AIDS 16:889–893
Massimi I, Ciuffetta A, Temperilli F, Ferrandino F, Zicari A, Pulcinelli FM et al (2015) Multidrug resistance protein-4 influences aspirin toxicity in human cell line. Mediat Inflamm 2015:607957
Massimi I, Guerriero R, Lotti LV, Lulli V, Borgognone A, Romani F et al (2014) Aspirin influences megakaryocytic gene expression leading to up-regulation of multidrug resistance protein-4 in human platelets. Br J Clin Pharmacol 78:1343–1353
Masunaga Y, Noto T, Suzuki K, Takahashi K, Shimizu Y, Morokata T (2007) Expression profiles of cytokines and chemokines in murine Mdr1a−/− colitis. Inflamm Res 56:439–446
Matsuo H, Takada T, Ichida K, Nakamura T, Nakayama A, Suzuki H et al (2011) ABCG2/BCRP dysfunction as a major cause of gout. Nucleosides Nucleotides Nucleic Acids 30:1117–11128
Matsuo H, Tsunoda T, Ooyama K, Sakiyama M, Sogo T, Takada T et al (2016) Hyperuricemia in acute gastroenteritis is caused by decreased urate excretion via ABCG2. Sci Rep 6:31003
Mattiello T, Guerriero R, Lotti LV, Trifirò E, Felli MP, Barbarulo A et al (2011) Aspirin extrusion from human platelets through multidrug resistance protein-4-mediated transport: evidence of a reduced drug action in patients after coronary artery bypass grafting. J Am Coll Cardiol 58:752–761
Mayer U, Wagenaar E, Beijnen JH, Smit JW, Meijer DK, van Asperen J et al (1996) Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr 1a P-glycoprotein. Br J Pharmacol 119:1038–1044
McGill MR, Jaeschke H (2013) Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res 30:2174–2187
Meijer OC, de Lange EC, Breimer DD, de Boer AG, Workel JO, de Kloet ER (1998) Penetration of dexamethasone into brain glucocorticoid targets is enhanced in mdr1A P-glycoprotein knockout mice. Endocrinology 139:1789–1793
Melguizo C, Prados J, Luque R, Ortiz R, Caba O, Álvarez PJ et al (2012) Modulation of MDR1 and MRP3 gene expression in lung cancer cells after paclitaxel and carboplatin exposure. Int J Mol Sci 13:16624–16635
Mendes J, Martinho A, Simoes O, Mota A, Breitenfeld L, Pais L (2009) Genetic polymorphism in CYP3A5 and MDR1 genes and their correlation with plasma levels of tacrolimus and cyclosporine in renal transplant recipients. Transplant Proc 41:840–842
Merino G, Alvarez AI, Pulido MM, Molina AJ, Schinkel AH, Prieto JG (2006) Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone antibiotics and affects theiroral availability, pharmacokinetics, and milk secretion. Drug Metab Dispos 34:690–695
Merino G, Jonker JW, Wagenaar E, van Herwaarden AE, Schinkel AH (2005) The breast cancer resistance protein (BCRP/ABCG2) affects pharmacokinetics, hepatobiliary excretion, and milk secretion of the antibiotic nitrofurantoin. Mol Pharmacol 67:1758–1764
Meyer Z, Schwabedissen HE, Grube M, Heydrich B, Linnemann K, Fusch C, Kroemer HK et al (2005) Expression, localization, and function of MRP5(ABCC5), a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts: effects of gestational age and cellular differentiation. Am J Pathol 166:39–48
Mistry P, Stewart AJ, Dangerfield W, Okiji S, Liddle C, Bootle D et al (2001) In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576. Cancer Res 61:749–758
Mitra P, Oskeritzian CA, Payne SG, Beaven MA, Milstien S, Spiegel S (2006) Role of ABC1 in export of sphingosine-1-phosphate from mast cells. Proc Natl Acad Sci U S A 103:16394–16399
Molday RS, Zhong M, Quazi F (2009) The Role of the photoreceptor ABC transporter ABCA4 in lipid transport and Stargardt Macular degeneration. Biochim Biophys Acta 1791:573–583
Moon C, Zhang W, Ren A, Arora K, Sinha C, Yarlagadda S et al (2015) Compartmentalized accumulation of cAMP near complexes of multidrug resistance protein 4 (MRP4) and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) contributes to drug-induced diarrhea. J Biol Chem 290:11246–11257
Morisaki K, Robey RW, Ozvegy-Laczka C, Honjo Y, Polgar O, Steadman K et al (2005) Single nucleotide polymorphisms modify the transporter activity of ABCG2. Cancer Chemother Pharmacol 56:161–172
Mouly S, Paine MF (2003) P-glycoprotein increases from proximal to distal regions of human small intestine. Pharm Res 20:1595–1599
Myint K, Li Y, James Paxton J, Mark McKeage M (2015) Multidrug resistance-associated protein 2 (MRP2) mediated transport of oxaliplatin-derived platinum in membrane vesicles. PLoS One 10:e0130727
Mueller CF, Afzal S, Becher UM, Wassmann S, Nickenig G, Wassmann K (2010) Role of the multidrug resistance protein-1 (MRP1) for endothelial progenitor cell function and survival. J Mol Cell Cardiol 49:482–489
Nakayama A, Matsuo H, Takada T, Ichida K, Nakamura T, Ikebuchi Y et al (2011) ABCG2 is a high-capacity urate transporter and its genetic impairment increases serum uric acid levels in humans. Nucleosides Nucleotides Nucleic Acids 30:1091–1097
Nakayama A, Matsuo H, Nakaoka H, Nakamura T, Nakashima H, Takada Y et al (2014) Common dysfunctional variants of ABCG2 have stronger impact on hyperuricemia progression than typical environmental risk factors. Sci Rep 4:5227
Newman MJ, Rodarte JC, Benbatoul KD, Romano SJ, Zhang C, Krane S et al (2000) Discovery and characterization of OC144-093, a novel inhibitor of P-glycoprotein-mediated multidrug resistance. Cancer Res 60:2964–2972
Niemeijer MN, van den Berg ME, Deckers JW, Aarnoudse AL, Hofman A, Franco OH et al (2015) ABCB1 gene variants, digoxin and risk of sudden cardiac death in a general population. Heart 101:1973–1979
Nicolaou M, Andress EJ, Zolnerciks JK, Dixon PH, Williamson C, Linton KJ (2012) Canalicular ABC transporters and liver disease. J Pathol 226:300–315
Nies AT, Keppler D (2007) The apical conjugate efflux pump ABCC2 (MRP2). Pflügers Arch 453:643–659
Nones K, Dommels YE, Martell S, Butts C, McNabb WC, Park ZA et al (2009a) The effects of dietary curcumin and rutin on colonic inflammation and gene expression in multidrug resistance gene-deficient (Mdr1a−/−) mice, a model of inflammatory bowel diseases. Br J Nutr 101:169–181
Nones K, Knoch B, Dommels YE, Paturi G, Butts C, McNabb WC et al (2009b) Multidrug resistance gene deficient (Mdr1a−/−) mice have an altered caecal microbiota that precedes the onset of intestinal inflammation. J Appl Microbiol 107:557–566
Nunoya K, Grant CE, Zhang D, Cole SP, Deeley RG (2003) Molecular cloning and pharmacological characterization of rat multidrug resistance protein 1 (mrp1). Drug Metab Dispos 31:1016–1026
Ogawa K, Suzuki H, Hirohashi T, Ishikawa T, Meier PJ, Hirose K et al (2000) Characterization of inducible nature of Mrp3 in rat liver. Am J Physiol Gastrointest Liver Physiol 278:G438–G446
Oh GS, Kim HJ, Shen A, Lee SB, Yang SH, Shim H et al (2016) New therapeutic concept of NAD redox balance for cisplatin nephrotoxicity. Biomed Res Int 2016:4048390
Oevermann L, Scheitz J, Starke K, Köck K, Kiefer T, Dölken G et al (2009) Hematopoietic stem cell differentiation affects expression and function of MRP4(ABCC4), a transport protein for signaling molecules and drugs. Int J Cancer 124:2303–2311
Okamura N, Hirai M, Tanigawara Y, Tanaka K, Yasuhara M, Ueda K et al (1993) Digoxin-cyclosporin A interaction: modulation of the multidrug transporter P-glycoprotein in the kidney. J Pharmacol Exp Ther 266:1614–1619
Oguri T, Bessho Y, Achiwa H, Ozasa H, Maeno K, Maeda H et al (2007) MRP8/ABCC11 directly confers resistance to 5-fluorouracil. Mol Cancer Ther 6:122–127
Oguri T, Isobe T, Suzuki T, Nishio K, Fujiwara Y, Katoh O et al (2000) Increased expression of the MRP5 gene is associated with exposure to platinum drugs in lung cancer. Int J Cancer 86:95–100
Ota I, Sakurai A, Toyoda Y, Morita S, Sasaki T, Chishima T et al (2010) Association between breast cancer risk and the wild-type allele of human ABC transporter ABCC11. Anticancer Res 30:5189–5194
Ota S, Ishii G, Goto K, Kubota K, Kim YH, Kojika M et al (2009) Immunohistochemical expression of BCRP and ERCC1 in biopsy specimen predicts survival in advanced non small cell lung cancer treated with cisplatin-based chemotherapy. Lung Cancer 64:98–104
Quazi F, Molday RS (2014) ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal. Proc Natl Acad Sci U S A 111:5024–5029
Oude Elferink RPJ, Paulusma CC (2007) Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein). Pflugers Arch 453:601–610
Panwala CM, Jones JC, Viney JL (1998) A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J Immunol 161:5733–5744
Peca D, Cutrera R, Masotti A, Boldrini R, Danhaive O (2015) ABCA3, a key player in neonatal respiratory transition and genetic disorders of the surfactant system. Biochem Soc Trans 43:913–919
Picchianti-Diamanti A, Rosado MM, Scarsella M, Laganà B, D’Amelio R (2014) P-glycoprotein and drug resistance in systemic autoimmune diseases. Int J Mol Sci 15:4965–4976
Piehler AP, Özcürümez M, Kaminski WE (2012) A-Subclass ATP-Binding Cassette Proteins in Brain Lipid Homeostasis and Neurodegeneration. Front Psych 3:17
Piñeiro R, Maffucci T, Falasca M (2011) The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. Oncogene 30:142–152
Plasschaert SL, de Bont ES, Boezen M, vander Kolk DM, Daenen SM, Faber KN et al (2005) Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia. Clin Cancer Res 11:8661–8668
Porro A, Haber M, Diolaiti D, Iraci N, Henderson M, Gherardi S et al (2010) Direct and coordinate regulation of ATP-binding cassette transporter genes by Myc factors generates specific transcription signatures that significantly affect the chemoresistance phenotype of cancer cells. J Biol Chem 285:19532–19543
Prasad KN, Cole WC, Yan XD, Nahreini P, Kumar B, Hanson A et al (2003) Defects in cAMP-pathway may initiate carcinogenesis in dividing nerve cells: a review. Apoptosis 8:579–586
Puntoni M, Sbrana F, Bigazzi F, Sampietro T (2012) Tangier disease: epidemiology, pathophysiology, and management. Am J Cardiovasc Drugs 12:303–311
Raggers RJ, Vogels I, van MG (2001) Multidrug-resistance P-glycoprotein (MDR1) secretes platelet-activating factor. Biochem J 357:859–865
Rahgozar S, Moafi A, Abedi M, Entezar-E-Ghaem M, Moshtaghian J, Ghaedi K et al (2014) mRNA expression profile of multidrug-resistant genes in acute lymphoblastic leukemia of children, a prognostic value for ABCA3 and ABCA2. Cancer Biol Ther 15:35–41
Rasmuson A, Kock A, Fuskevåg OM, Kruspig B, Simón-Santamaría J, Gogvadze V et al (2012) Autocrine prostaglandin E2 signaling promotes tumor cell survival and proliferation in childhood neuroblastoma. PLoS One 7:e29331
Rengelshausen J, Göggelmann C, Burhenne J, Riedel KD, Ludwig J, Weiss J et al (2003) Contribution of increased oral bioavailability and reduced nonglomerular renal clearance of digoxin to the digoxin-clarithromycin interaction. Br J Clin Pharmacol 56:32–38
Rijavec M, Šilar M, Triller N, Kern I, Čegovnik U, Košnik M et al (2011) Expressions of topoisomerase IIα and BCRP in metastatic cells are associated with overall survival in small cell lung cancer patients. Pathol Oncol Res 17:691–696
Robey RW, Honjo Y, Morisaki K, Nadjem TA, Runge S, Risbood M et al (2003) Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity. Bri J Cancer 89:1971–1978
Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kélaïdi C, Blanche P (2004) Acute colchicine intoxication during clarithromycin administration. Ann Pharmacother 38:2074–2077
Schaeffeler E, Eichelbaum M, Brinkmann U, Penger A, Asante-Poku S, Zanger UM et al (2001) Frequency of C3435T polymorphism of MDR1 gene in African people. Lancet 358:383–384
Sakaeda T, Nakamura T, Horinouchi M, Kakumoto M, Ohmoto N, Sakai T et al (2001) MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects. Pharm Res 18:1400–1404
Salimizand H, Amini S, Abdi M, Ghaderi B, Azadi NA (2016) Concurrent effects of ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp genetic polymorphisms with risk of cancer, clinical output, and response to treatment with imatinib mesylate in patients with chronic myeloid leukemia. Tumor Biol 37:791–798
Sanchez S, Jimenez C, Carrera AC, Diaz-Nido J, Avila J, Wandosell F (2004) A cAMP-activated pathway, including PKA and PI3K, regulates neuronal differentiation. Neurochem Int 44:231–242
Schaich M, Soucek S, Thiede C, Ehninger G, Illmer T (2005) MDR1 and MRP1 gene expression are independent predictors for treatment outcome in adult acute myeloid leukaemia. Br J Haemato 128:324–332
Scharenberg CW, Harkey MA, Torok-Storb B (2002) The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood 99:507–512
Schinkel AH, Smit JJ, van Tellingen O, Beijnen JH, Wagenaar E, van Deemter L et al (1994) Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994(77):491–450
Schinkel AH, Jonker JW (2012) Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev 64:138–153
Schuetz JD, Connelly MC, Sun D, Paibir SG, Flynn PM, Srinivas RV et al (1999) MRP4: a previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nat Med 5:1048–1051
Schulz T, Schumacher U, Christian Prante C, Sextro W, Prehm P (2010) Cystic fibrosis transmembrane conductance regulator can export hyaluronan. Pathobiology 77:200–209
Schulz T, Schumacher U, Prehm P (2007) Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular cGMP. J Biol Chem 282:20999–21004
Scialis RJ, Csanaky IL, IL GMJ, Manautou JE (2015) Multidrug resistance- associated protein 3 plays an important role in protection against acute toxicity of diclofenac. Drug Metab Dispos 43:944–950
Scott CA, Rajpopat S, Di WL (2013) Harlequin ichthyosis: ABCA12 mutations underlie defective lipid transport, reduced protease regulation and skin-barrier dysfunction. Cell Tissue Res 351:281–288
Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY et al (1985) Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med 313:1111–1116
Seelheim P, Wüllner A, Galla HJ (2013) Substrate translocation and stimulated ATP hydrolysis of human ABC transporter MRP3 show positive cooperativity and are half-coupled. Biophys Chem 171:3–37
Semsei AF, Erdelyi DJ, Ungvari I, Csagoly E, Hegyi MZ, Kiszel PS et al (2012) ABCC1 polymorphisms in anthracycline-induced cardiotoxicity in childhood acute lymphoblastic leukaemia. Cell Biol Int 36:79–86
Seyffer F, Tampé R (2015) ABC transporters in adaptive immunity. Biochim Biophys Acta 1850:449–460
Shafran A, Ifergan I, Bram E, Jansen G, Kathmann I et al (2005) ABCG2 harboring the Gly482 mutation confers high-level resistance to various hydrophilic antifolates. Cancer Res 65:8414–8422
Shen S, Callaghan D, Juzwik C, Xiong H, Huang P, Zhang W (2010) ABCG2 reduces ROS-mediated toxicity and inflammation: a potential role in Alzheimer’s disease. J Neurochem 114:1590–1604
Shord SS, Thompson DM, Krempl GA, Hanigan MH (2006) Effect of concurrent medications on cisplatin-induced nephrotoxicity in patients with head and neck cancer. Anti-Cancer Drugs 17:207–215
Sicchieri RD, da Silveira WA, Raque L, Mandarano M, de Oliveira TMG, Carrara HHA et al (2015) ABCG2 is a potential marker of tumor-initiating cells in breast cancer. Tumor Biol 36:9233–9243
Siedlinski M, Boezen HM, Boer JM, Smit HA, Postma DS (2009) ABCC1 polymorphisms contribute to level and decline of lung function in two population-based cohorts. Pharmacogenet Genomics 19:675–684
Siegsmund M, Brinkmann U, Scháffeler E, Weirich G, Schwab M, Eichelbaum et al (2002) Association of the P-glycoprotein transporter MDR1 (C3435T) polymorphism with the susceptibility to renal epithelial tumors. J Am Soc Nephrol 13:1847–1854
Sigal N, Kaplan Zeevi M, Weinstein S, Peer D, Herskovits AA (2015) The human P-glycoprotein transporter enhances the type I interferon response to Listeria monocytogenes infection. Infect Immun 83:2358–2368
Singh R, Srivastava A, Kapoor R, Mittal RD (2011) Do drug transporter(ABCB1) SNPs influence cyclosporine and tacrolimus dose requirements and renal allograft outcome in the posttransplantation period? J Clin Pharmacol 51:603–615
Slot AJ, Molinski SV, Cole SP (2011) Mammalian multidrug-resistance proteins (MRPs). Essays Biochem 50:179–207
Slot AJ, Wise DD, Deeley RG, Monks TJ, Cole SP (2008) Modulation of human multidrug resistance protein (MRP) 1 (ABCC1) and MRP2 (ABCC2) transport activities by endogenous and exogenous glutathione-conjugated catechol metabolites. Drug Metab Dispos 36:552–560
Smit JW, Huisman MT, van Tellingen O, Wiltshire HR, Schinkel AH (1999) Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure. J Clin Invest 104:1441–1447
Solazzo M, Fantappiè O, Lasagna N, Sassoli C, Nosi D, Mazzanti R (2006) P-GP localization in mitochondria and its functional characterization in multiple drug-resistant cell lines. Exp Cell Res 312:4070–4078
Solazzo M, Fantappie O, Amico MD, Sassoli C, Tani A, Cipriani G et al (2009) Mitochondrial expression and functional activity of breast cancer resistance protein in different multiple drug-resistant cell lines. Cancer Res 69:7235–7242
Song S, Suzuki H, Kawai R, Sugiyama Y (1999) Effect of PSC 833, a P-glycoprotein modulator, on the disposition of vincristine and digoxin in rats. Drug Metab Dispos 27:689–694
Soroka CJ, Boyer JL (2014) Biosynthesis and trafficking of the bile salt export pump, BSEP: therapeutic implications of BSEP mutations. Mol Asp Med 37:3–14
Sparreboom A, van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DK et al (1997) Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci U S A 94:2031–2035
Stapelbroek JM, van Erpecum KJ, Klomp LWJ, Houwen RHJ (2010) Liver disease associated with canalicular transport defects: Current and future therapies. J Hepatol 52:258–271
Stephens RH, Tanianis-Hughes J, Higgs NB, Humphrey M, Warhurst G (2002) Region-dependent modulation of intestinal permeability by drug efflux transporters: in vitro studies in Mdr1a(−/−) mouse intestine. J Pharmacol Exp Ther 303:1095–1101
Surowiak P, Materna V, Kaplenko I, Spaczynski M, Dolinska-Krajewska B, Gebarowska E et al (2006) ABCC2 (MRP2, cMOAT) can be localized in the nuclear membrane of ovarian carcinomas and correlates with resistance to cisplatin and clinical outcome. Clin Cancer Res 12:7149–1458
Tachibana T, Kitamura S, Kato M, Mitsui T, Shirasaka Y, Yamashita S et al (2010) Model analysis of the concentration-dependent permeability of P-GP substrates. Pharm Res 27:442–446
Takada T, Ichida K, Matsuo H, Nakayama A, Murakami K, Yamanashi Y et al (2014) ABCG2 dysfunction increases serum uric acid by decreased intestinal urate excretion. Nucleosides Nucleotides Nucleic Acids 33:275–281
Takeichi T, Hsu CK, Yang HS, Chen HY, Wong TW, Tsai WL et al (2015) Progressive hyperpigmentation in a Taiwanese child due to an inborn error of vitamin B12 metabolism. Br J Dermatol 172:1111–1115
Tamura A, Watanabe M, Saito H, Nakagawa H, Kamachi T, Okura et al (2006) Functional validation of the genetic polymorphisms of human ATP-binding cassette (ABC) transporter ABCG2: identification of alleles that are defective in porphyrin transport. Mol Pharmacol 70:287–296
Tamura M, Kondo M, Horio M, Ando M, Saito H, Yamamoto M et al (2012) Genetic polymorphisms of the adenosine triphosphate-binding cassette transporters (ABCG2, ABCB1) and gefitinib toxicity. Nagoya J Med Sci 74:133–140
Tanabe M, Ieiri I, Nagata N, Inoue K, Ito S, Kanamori Y et al (2001) Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. J Pharmacol Exp Ther 297:1137–1143
Tanfin Z, Serrano-Sanchez M, Leiber D (2011) ATP-binding cassette ABCC1 is involved in the release of sphingosine 1-phosphate from rat uterine leiomyoma ELT3 cells and late pregnant rat myometrium. Cell Signal 23:1997–2004
Tang K, Ngoi SM, Gwee PC, Chua JM, Lee EJ, Chong SS et al (2002) Distinct haplotype profiles and strong linkage disequilibrium at the MDR1 multidrug transporter gene locus in three ethnic Asian populations. Pharmacogenetics 12:437–450
Tarling EJ, de Aguiar Vallim TQ, Edwards PA (2013) Role of ABC transporters in lipid transport and human disease. Trends Endocrinol Metab 24:342–350
Tchernychev B, Ge P, Kessler MM, Solinga RM, Wachtel D, Tobin JV et al (2015) MRP4 modulation of the guanylate cyclase–C/cGMP pathway: effects on linaclotide-induced electrolyte secretion and cGMP efflux. J Pharmacol Exp Ther 355:48–56
Temperilli F, Franco MD, Massimi I, Guarino ML, Guzzo MP, Valesini G et al (2016) Nonsteroidal anti-inflammatory drugs in-vitro and in-vivo treatment and multidrug resistance protein 4 expression in human platelets. Vasc Pharmacol 76:11–17
Thévenod F, Friedmann JM, Katsen AD, Hauser IA (2000) Up-regulation of multidrug resistance P-glycoprotein via nuclear factor-kappaB activation protects kidney proximal tubule cells from cadmium- and reactive oxygen species-induced apoptosis. Biol Chem 275:1887–1896
Thomas AC, Cullup T, Norgett EE, Hill T, Barton S, Dale BA et al (2006) ABCA12 is the major harlequin ichthyosis gene. J Invest Dermatol 126:2408–2413
Tiribelli M, Fabbro D, Franzoni A, Fanin R, Damante G, Damiani D (2013) Q141K polymorphism of ABCG2 protein is associated with poor prognosis in adult acute myeloid leukemia treated with idarubicin-based chemotherapy. Haematologica 98:e28–e29
Tiwari AK, Sodani K, Dai CL, Abuznait AH, Singh S, Xiao ZJ et al (2013) Nilotinib potentiates anticancer drug sensitivity in murine ABCB1-, ABCG2-, and ABCC10-multidrug resistance xenograft models. Cancer Lett 328:307–317
Tomonari T, Takeishi S, Taniguchi T, Tanaka T, Tanaka H, Fujimoto S et al (2016) MRP3 as a novel resistance factor for sorafenib in hepatocellular carcinoma. Oncotarget 7: 7204–7217
Toyoda Y, Ishikawa T (2010) Pharmacogenomics of Human ABC Transporter ABCC11 (MRP8): Potential Risk of Breast Cancer and Chemotherapy Failure Anticancer Agents. Med Chem 10:617–624
Tsuruoka S, Sugimoto KI, Fujimura A, Imai M, Asano Y, Muto S (2001) P-glycoprotein-mediated drug secretion in mouse proximal tubule perfused in vitro. J Am Soc Nephrol 12:177–181
Tsybovsky Y, Molday RS, Palczewski K (2010) The ATP-binding cassette transporter ABCA4: structural and functional properties and role in retinal disease. Adv Exp Med Biol 703:105–125
Uemura T, Oguri T, Ozasa H, Takakuwa O, Miyazaki M, Maeno K et al (2010) ABCC11/MRP8 confers pemetrexed resistance in lung cancer. Cancer Sci 101:2404–2410
Ulrich DL, Lynch J, Wang Y, Fukuda Y, Nachagari D, Du G et al (2012) ATP-dependent mitochondrial porphyrin importer ABCB6 protects against phenylhydrazine toxicity. J Biol Chem 287:12679–12690
Ushijima R, Takayama K, Izumi M, Harada T, Horiuchi Y, Uchino J et al (2007) Immunohistochemical expression of MRP2 and clinical resistance to platinum-based chemotherapy in small cell lung cancer. Anticancer Res 27:4351–4358
Vallakati A, Chandra PA, Pednekar M, Frankel R, Shani J (2013) Dronedarone- induced digoxin toxicity: new drug, new interactions. Am J Ther 20:e717–e719
van Asperen J, van Tellingen O, Beijnen JH (2000) The role of mdr1a P-glycoprotein in the biliary and intestinal secretion of doxorubicin and vinblastine in mice. Drug Metab Dispos 28:264–267
van der Deen M, Marks H, Willemse BW, Postma DS, Müller M, Smit EF et al (2006) Diminished expression of multidrug resistance-associated protein 1 (MRP1) in bronchial epithelium of COPD patients. Virchows Arch 449:682–688
van Herwaarden AE, Jonker JW, Wagenaar E, Brinkhuis RF, Schellens JH, Beijnen JH et al (2003) The breast cancer resistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Res 63:6447–6452
van Herwaarden AE, Wagenaar E, Karnekamp B, Merino G, Jonker JW, Schinkel AH (2006) Breast cancer resistance protein (Bcrp1/Abcg2) reduces systemic exposure of the dietary carcinogens aflatoxin B1, IQ and Trp-P-1 but also mediates their secretion into breast milk. Carcinogenesis 27:123–130
van Tellingen O, Buckle T, Jonker JW, van der Valk MA, Beijnen JH (2003) P-glycoprotein and Mrp1 collectively protect the bone marrow from vincristine-induced toxicity in vivo. Br J Cancer 89:1776–1782
Vanwijngaerden YM, Wauters J, Langouche L, Vander Perre S, Liddle C, Setal C (2011) Critical illness evokes elevated circulating bile acids related to altered hepatic transporter and nuclear receptor expression. Hepatology 54:1741–1752
Verstuyft C, Schwab M, Schaeffeler E, Kerb R, Brinkmann U, Jaillon P et al (2003) Digoxin pharmacokinetics and MDR1 genetic polymorphisms. Eur J Clin Pharmacol 58:809–812
Vlaming ML, Mohrmann K, Wagenaar E, de Waart DR, Elferink RP, Lagas JS et al (2006) Carcinogen and anticancer drug transport by Mrp2 in vivo: study using Mrp2 (Abcc2) knockout mice. J Pharmacol Exp Ther 318:319–327
Vlaming ML, van Esch A, van de Steeg E, Pala Z, Wagenaar E, van Tellingen O et al (2011) Impact of Abcc2 [multidrug resistance-associated protein (mrp) 2], abcc3 (mrp3), and abcg2 (breast cancer resistance protein) on the oral pharmacokinetics of methotrexate and its main metabolite 7-hydroxymethotrexate. Drug Metabo Dispos 39:1338–1344
Volk EL, Schneider E (2003) Wild-Type Breast cancer resistance protein (BCRP/ABCG2) is a Methotrexate Polyglutamate Transporter. Cancer Res 63:5538–5543
Vulsteke C, Pfeil AM, Maggen C, Schwenkglenks M, Pettengell R, Szucs et al (2015) Clinical and genetic risk factors for epirubicin-induced cardiac toxicity in early breast cancer patients. Breast Cancer Res Treat1 52:67–76
Walle UK, Walle T (1998) Taxol transport by human intestinal epithelial Caco-2 cells. Drug Metab Dispos 26:343–346
Wambach JA, Casey AM, Fishman MP, Wegner DJ, Wert SE, Cole FS et al (2014) Genotype-phenotype correlations for infants and children with ABCA3 deficiency. Am J Respir Crit Care Med 189:1538–1543
Wang F, Zhou F, Kruh GD, Gallo JM (2010a) Influence of blood-brain barrier efflux pumps on the distribution of vincristine in brain and brain tumors. Neuro-Oncology 12:1043–1049
Wang J, Zhang M, Zhang L, Cai H, Zhou S, Zhang J et al (2010b) Correlation of Nrf2, HO-1, and MRP3 in gallbladder cancer and their relationships to clinicopathologic features and survival. J Surg Res 164:199–105
Wang R, Chen HL, Liu L, Sheps JA, Phillips MJ, Ling V (2009) Compensatory role of P-glycoproteins in knockout mice lacking the bile salt export pump. Hepatology 50:948–956
Wang YH, Chao PD, Hsiu SL, Wen KC, Hou YC (2004) Lethal quercetin-digoxin interaction in pig. Life Sci 74:1191–1197
Weidner LD, Fung KL, Kannan P, Moen JK, Kumar JS, Mulder J et al (2016) Tariquidar is an inhibitor and not a substrate of human and mouse P-glycoprotein. Drug Metab Dispos 44:275–282
Wen X, Buckley B, McCandlish E, Goedken MJ, Syed S, Pelis R et al (2014) Transgenic expression of the human MRP2 transporter reduces cisplatin accumulation and nephrotoxicity in Mrp2-null mice. Am J Pathol 184:1299–1308
Wen J, Luo J, Huang W, Tang J, Zhou H, Zhang W (2015) The pharmacological and physiological roles of multidrug-resistant protein 4. J Pharmacol Exp Ther 354:358–375
Wetterich U, Spahn-Langguth H, Mutschler E, Terhaag B, Rösch W, Langguth P (1996) Evidence for intestinal secretion as an additional clearance pathway of talinolol enantiomers: concentration- and dose-dependent absorption in vitro and in vivo. Pharm Res 13:514–552
Widder JD, Guzik TJ, Mueller CF, Clempus RE, Schmidt HH, Dikalov SI et al (2007) Role of the multidrug resistance protein-1 in hypertension and vascular dysfunction caused by angiotensin II. Arterioscler Thromb Vasc Biol 27:762–768
Wijnholds J, Scheffer GL, van der Valk M, van der Valk P, Beijnen JH, Scheper RJ et al (1998) Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage. J Exp Med 188:797–808
Wijnholds J, deLange EC, Scheffer GL, van den Berg DJ, Mol CA, van der Valk M et al (2000) Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier. J Clin Invest 105:279–285
Woodward OM, A Köttgen A, Köttgen M (2011) ABCG transporters and disease. FEBS J 278:3215–3225
Wu H, Liu Y, Kang H, Xiao Q, Yao W, Zhao H et al (2015) Genetic variations in ABCG2 gene predict beast carcinoma susceptibility and clinical outcomes after treatment with anthracycline-based chemotherapy. Biomed Res Int 2015:279109
Xiong H, Callaghan D, Jones A, Bai J, Rasquinha I, Smith C et al (2009) ABCG2 is upregulated in Alzheimer’s brain with cerebral amyloid angiopathy and may act as a gatekeeper at the blood-brain barrier for Abeta(1-40) peptides. J Neurosci 29:5463–5475
Yamada A, Ishikawa T, Ota I, Kimura M, Shimizu D, Tanabe M et al (2013) High expression of ATP-binding cassette transporter ABCC11 in breast tumors is associated with aggressive subtypes and low disease-free survival. Breast Cancer Res Treat 137:773–782
Yamasaki M, Makino T, Masuzawa T, Kurokawa Y, Miyata H, Takiguchi S et al (2011) Role of multidrug resistance protein 2 (MRP2) in chemoresistance and clinical outcome in oesophageal squamous cell carcinoma. Brit J cancer 104:707–713
Yang G, Wang XJ, Huang LJ, Zhou YA, Tian F, Jin-Bo Zhao JB et al (2015) High ABCG4 Expression is associated with poor prognosis in non-small-cell lung cancer patients treated with cisplatin-based chemotherapy. PLoS One 10:e0135576
Yoh K, Ishii G, Yokose T, Minegishi Y, Tsuta K, Goto K et al (2004) Breast cancer resistance protein impacts clinical outcome in platinum-based chemotherapy for advanced non-small cell lung cancer. Clin Cancer Res 10:1691–1697
Yoshioka M, Sagara H, Takahashi F, Harada N, Nishio K, Mori A et al (2009) Role of multidrug resistance-associated protein 1 in the pathogenesis of allergic airway inflammation. Am J Physiol Lung Cell Mol Physiol 296:L30–L36
Yoshikado T, Takada T, Yamamoto T, Yamaji H, Ito K et al (2011) Itraconazole-induced cholestasis: involvement of the inhibition of bile canalicular phospholipid translocator MDR3/ABCB4. Mol Pharmacol 79:241–250
Yu S, Yu Y, Liu L, Wang X, Lu S, Liang Y et al (2010) Increased plasma exposures of five protoberberine alkaloids from Coptidis Rhizoma in streptozotocin-induced diabetic rats: is P-GP involved? Planta Med 76:876–881
Yu XH, Qian K, Jiang N, Zheng XL, Cayabyab FS, Tang CK (2014) ABCG5/ABCG8 in cholesterol excretion and atherosclerosis. Clin Chim Acta 428:82–88
Yuan Y, Yang Z, Miao X, Li D, Liu Z, Zou Q (2015) The clinical significance of FRAT1 and ABCG2 expression in pancreatic ductal adenocarcinoma. Tumor Biol 36:9961–9968
Yvan-Charvet L, Wang N, Tall AR (2010) The role of HDL, ABCA1 and ABCG1 transporters in cholesterol efflux and immune responses. Arterioscler Thromb Vasc Biol 30:139–143
Zalups RK, Joshee L, Christy C, Bridges CC (2014) Novel Hg2+-induced nephropathy in rats and mice lacking mrp2: evidence of axial heterogeneity in the handling of Hg2+ along the proximal tubule. Toxicol Sci 142:250–260
Zelcer N, Huisman MT, Reid G, Wielinga P, Breedveld P, Kuil A et al (2003) Evidence for two interacting ligand binding sites in human multidrug resistance protein 2 (ATP binding cassette C2). J Biol Chem 278:23538–23544
Zelcer N, van de Wetering K, de Waart R, Scheffer GL, Marschall HU, Wielinga PR et al (2006) Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides. J Hepatolo 44:768–775
Zelcer N, van de Wetering K, Hillebrand M, Sarton E, Kuil A, Wielinga PR et al (2005) Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. Proc Natl Acad Sci U S A 102:7274–7279
Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P (2001) Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem 276:46400–46407
Zeng H, Liu G, Rea PA, Kruh GD (2000) Transport of amphipathic anions by human multidrug resistance protein 3. Cancer Res 60:4779–4784
Zimmermann C, van de Wetering K, van de Steeg E, Wagenaar E, Vens C, Schinkel AH (2008) Species-dependent transport and modulation properties of human and mouse multidrug resistance protein 2 (MRP2/Mrp2, ABCC2/Abcc2). Drug Metab Dispos 36:631–640
Zhang J, Zhou F, Wu X, Zhang X, Chen Y, Zha BS et al (2012) Cellular pharmacokinetic mechanisms of adriamycin resistance and its modulation by 20(S)-ginsenoside Rh2 in MCF-7/Adr cells. Br J Pharmacol 165:120–134
Zhang W, Deng J, Sunkara M, Morris AJ, Wang C, St Clair D et al (2015) Loss of multidrug resistance-associated protein 1 potentiates chronic doxorubicin-induced cardiac dysfunction in mice. J Pharmacol Exp Ther 355:280–287
Zhao X, Guo Y, Yue W, Zhang L, Gu M, Wang Y (2014) ABCC4 is required for cell proliferation and tumorigenesis in non-small cell lung cancer. OncoTargets Ther 7:343–351
Zhou S, Morris JJ, Barnes Y, Lan L, Schuetz JD, Sorrentino BP (2002) Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc Natl Acad Sci U S A 99:12339–11244
Zhou L, Schmidt K, Nelson FR, Zelesky V, Troutman MD, Feng B (2009) The effect of breast cancer resistance protein and P-glycoprotein on the brain penetration of flavopiridol, imatinib mesylate (Gleevec), prazosin, and 2-methoxy-3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)propanoic acid (PF-407288) in mice. Drug Metab Dispos 37:946–955
Zhou S, Zong Y, Ney PA, Nair G, Stewart CF, Sorrentino BP (2005) Increased expression of the Abcg2 transporter during erythroid maturation plays a role in decreasing cellular protoporphyrin IX level. Blood 105:2571–2576
Zollmann T, Moiset G, Tumulka F, Tampé R, Poolman B, Abele R (2015) Single liposome analysis of peptide translocation by the ABC transporter TAPL. Proc Natl Acad Sci U S A 112:2046–2051
Zutz A, Gompf S, Schägger H, Tampé R (2009) Mitochondrial ABC proteins in health and disease. Biochim Biophys Acta 1787:681–690
Zyss J, Béhin A, Couvert P, Bouhour F, Sassolas A, Kolev I et al (2012) Clinical and electrophysiological characteristics of neuropathy associated with Tangier disease. J Neurol 259:1222–1226
Acknowledgments
The project was in part supported by the National Natural Science Foundation of China (No. 81872930; 81573490) and “Double First-Class” University project (No. CPU2018GY22).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Liu, X. (2019). ABC Family Transporters. In: Liu, X., Pan, G. (eds) Drug Transporters in Drug Disposition, Effects and Toxicity. Advances in Experimental Medicine and Biology, vol 1141. Springer, Singapore. https://doi.org/10.1007/978-981-13-7647-4_2
Download citation
DOI: https://doi.org/10.1007/978-981-13-7647-4_2
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-7646-7
Online ISBN: 978-981-13-7647-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)