929
Views
48
CrossRef citations to date
0
Altmetric
Review

New insights in the biology of ABC transporters ABCC2 and ABCC3: impact on drug disposition

, , &

Bibliography

  • Klein I, Sarkadi B, Váradi A. An inventory of the human ABC proteins. Biochim Biophys Acta 1999;1461:237-62
  • 49 Human ATP-binding Cassette Transporters. Müller M. Nutrition, metabolism and genomics group. Wageningen, Netherlands; 2001. Available from: http://nutrigene.4t.com/humanabc.htm
  • Cole SP, Bhardwaj G, Gerlach JH, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 1992;258:1650-4
  • Nishimura M, Naito S. Tissue-specific mRNA expression profiles of human ATP-binding cassette and solute carrier transporter superfamilies. Drug Metab Pharmacokinet 2005;20:452-77
  • Váradi A, Sarkadi B. Multidrug resistance-associated proteins: export pumps for conjugates with glutathione, glucuronate or sulfate. Biofactors 2003;17:103-14
  • Mayer R, Kartenbeck J, Buchler M, et al. Expression of the MRP gene-encoded conjugate export pump in liver and its selective absence from the canalicular membrane in transport-deficient mutant hepatocytes. J Cell Biol 1995;131:137-50
  • Paulusma CC, Bosma PJ, Zaman GJ, et al. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science 1996;271:1126-8
  • Jansen PL, Peters WH, Lamers WH. Hereditary chronic conjugated hyperbilirubinemia in mutant rats caused by defective hepatic anion transport. Hepatology 1985;5:573-9
  • Hosokawa S, Tagaya O, Mikami T, et al. A new rat mutant with chronic conjugated hyperbilirubinemia and renal glomerular lesions. Lab Anim Sci 1992;42:27-34
  • Ito K, Suzuki H, Hirohashi T, et al. Expression of a putative ATP-binding cassette region, homologous to that in multidrug resistance-associated protein (MRP), is hereditarily defective in eisai hyperbilirubinemic rats (EHBR). Int Hepatol Commun 1996;4:291-8
  • Jedlitschky G, Hoffmann U, Kroemer HK. Structure and function of the MRP2 (ABCC2) protein and its role in drug disposition. Expert Opin Drug Metab Toxicol 2006;2:351-66
  • Nies AT, Keppler D. The apical conjugate efflux pump ABCC2 (MRP2). Pflugers Arch 2007;453:643-59
  • Dubin IN, Johnson FB. Chronic idiopathic jaundice with unidentified pigment in liver cells; a new clinicopathologic entity with a report of 12 cases. Medicine 1954;33:155-97
  • Kitamura T, Alroy J, Gatmaitan Z, et al. Defective biliary excretion of epinephrine metabolites in mutant (TR−) rats: Relation to the pathogenesis of black liver in the dubin‐johnson syndrome and corriedale sheep with an analogous excretory defect. Hepatology 1992;15:1154-9
  • Meier Y, Zodan T, Lang C, et al. Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump. World J Gastroenterol 2008;14:38-45
  • Suzuki H, Sugiyama Y. Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): its impact on drug disposition. Adv Drug Deliv Rev 2002;54:1311-31
  • Fromm MF, Kauffmann HM, Fritz P, et al. The effect of rifampin treatment on intestinal expression of human MRP transporters. Am J Pathol 2000;157:1575-80
  • Sasaki M, Suzuki H, Ito K, et al. Transcellular transport of organic anions across a double-transfected madin–Darby canine kidney II cell monolayer expressing both human organic anion-transporting polypeptide (OATP2/SLC21A6) and multidrug resistance-associated protein 2 (MRP2/ABCC2). J.Biol.Chem 2002;277:6497-503
  • Narasaki F, Oka M, Nakano R, et al. Human canalicular multispecific organic anion transporter (cMOAT) is expressed in human lung, gastric, and colorectal cancer cells. Biochem Biophys Res Commun 1997;240:606-11
  • Sandusky GE, Mintze KS, Pratt SE, et al. Expression of multidrug resistance-associated protein 2 (MRP2) in normal human tissues and carcinomas using tissue microarrays. Histopathology 2002;41:65-74
  • van der Kolk DM, de Vries EG, Koning JA, et al. Activity and expression of the multidrug resistance proteins MRP1 and MRP2 in acute myeloid leukemia cells, tumor cell lines, and normal hematopoietic CD34+ peripheral blood cells. Clin Cancer Res 1998;4:1727-36
  • Cui Y, König J, Buchholz U, et al. Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells. Mol Pharmacol 1999;55:929-37
  • Chu X, Kato Y, Niinuma K, et al. Multispecific organic anion transporter is responsible for the biliary excretion of the camptothecin derivative irinotecan and its metabolites in rats. J Pharmacol Exp Ther 1997;281:304-14
  • Huisman MT, Chhatta AA, van Tellingen O, et al. MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid. Int J Cancer 2005;116:824-9
  • Hirohashi T, Suzuki H, Ito K, et al. Hepatic expression of multidrug resistance-associated protein-like proteins maintained in eisai hyperbilirubinemic rats. Mol Pharmacol 1998;53:1068-75
  • Uchiumi T, Hinoshita E, Haga S, et al. Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport. Biochem Biophys Res Commun 1998;252:103-10
  • Kool M, de Haas M, Scheffer GL, et al. 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 1997;57:3537-47
  • Belinsky MG, Bain LJ, Balsara BB, et al. Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. J Natl Cancer Inst 1998;90:1735-41
  • Kiuchi Y, Suzuki H, Hirohashi T, et al. cDNA cloning and inducible expression of human multidrug resistance associated protein 3 (MRP3). FEBS Lett 1998;433:149-52
  • Hirohashi T, Suzuki H, Takikawa H, et al. ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (Mrp3). J Biol Chem 2000;275:2905-10
  • Lagas JS, Fan L, Wagenaar E, et al. P-glycoprotein (P-gp/Abcb1), Abcc2, and Abcc3 determine the pharmacokinetics of etoposide. Clin Cancer Res 2010;16:130-40
  • Kool M, van der Linden M, de Haas M, et al. MRP3, an organic anion transporter able to transport anti-cancer drugs. P Natl Acad Sci USA 1999;96:6914-19
  • Scheffer GL, Kool M, de Haas M, et al. Tissue distribution and induction of human multidrug resistant protein 3. Lab Invest 2002;82:193-201
  • Konig J, Rost D, Cui Y, Keppler D. Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane. Hepatology 1999;29:1156-63
  • Rost D, Mahner S, Sugiyama Y, et al. Expression and localization of the multidrug resistance-associated protein 3 in rat small and large intestine. Am J Physiol Gastrointest Liver Physiol 2002;282:720-6
  • Shoji T, Suzuki H, Kusuhara H, et al. ATP-dependent transport of organic anions into isolated basolateral membrane vesicles from rat intestine. Am J Physiol Gastrointest Liver Physiol 2004;287:749-56
  • Zelcer N, van de Wetering K, Hillebrand M, et al. Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. P Natl Acad Sci USA 2005;102:7274-9
  • Soroka CJ, Lee JM, Azzaroli F, et al. Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver. Hepatology 2001;33:783-91
  • Kubo K, Sekine S, Saito M. Compensatory expression of MRP3 in the livers of MRP2-deficient EHBRs is promoted by DHA intake. Biosci BiotechnolBiochem 2009;73:2432-8
  • Keppler D. The roles of MRP2, MRP3, OATP1B1, and OATP1B3 in conjugated hyperbilirubinemia. Drug Metab Dispos 2014;42:561-5
  • Nies AT, König J, Pfannschmidt M, et al. Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma. Int J Cancer 2001;94:492-9
  • Ohishi Y, Oda Y, Uchiumi T, et al. ATP-binding cassette superfamily transporter gene expression in human primary ovarian carcinoma. Clin Cancer Res 2002;8:3767-75
  • Plasschaert SL, de Bont ES, Boezen M, et al. Expression of multidrug Resistance–Associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia. Clin Cancer Res 2005;11:8661-8
  • Zelcer N, Saeki T, Reid G, et al. Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem 2001;276:46400-7
  • Ostrow J. Bile pigments and jaundice - molecular, metabolic and medical aspects. Marcel Dekker Inc; New York: 1986
  • Cui Y, Konig J, Leier I, et al. Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. J Biol Chem 2001;276:9626-30
  • van de Steeg E, Stranecky V, Hartmannova H, et al. Complete OATP1B1 and OATP1B3 deficiency causes human rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest 2012;122:519-28
  • Jansen PL, Bosma PJ, Chowdhury JR. Molecular biology of bilirubin metabolism. Prog Liver Dis 1995;13:125-50
  • Mackenzie PI, Owens IS, Burchell B, et al. The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics 1997;7:255-69
  • Bosma PJ, Chowdhury JR, Bakker C, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in gilbert’s syndrome. N Engl J Med 1995;333:1171-5
  • Nathanson MH, Boyer JL. Mechanisms and regulation of bile secretion. Hepatology 1991;14:551-66
  • Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 2003;83:633-71
  • Ito K, Suzuki H, Sugiyama Y. Single amino acid substitution of rat MRP2 results in acquired transport activity for taurocholate. Am J Physiol Gastrointest Liver Physiol 2001;281:G1034-43
  • Kuipers F, Enserink M, Havinga R, et al. Separate transport systems for biliary secretion of sulfated and unsulfated bile acids in the rat. J Clin Invest 1988;81:1593-9
  • Kuipers F, Radominska A, Zimniak P, et al. Defective biliary secretion of bile acid 3-O-glucuronides in rats with hereditary conjugated hyperbilirubinemia. J Lipid Res 1989;30:1835-45
  • Hofmann AF. Bile acids: the good, the bad, and the ugly. News Physiol Sci 1999;14:24-9
  • Kullak-ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 2004;126:322-42
  • Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 2003;72:137-74
  • Redinger RN. Nuclear receptors in cholesterol catabolism: molecular biology of the enterohepatic circulation of bile salts and its role in cholesterol homeostasis. J Lab Clin Med 2003;142:7-20
  • Redinger RN. The coming of age of our understanding of the enterohepatic circulation of bile salts. Am J Surg 2003;185:168-72
  • Redinger RN. The role of the enterohepatic circulation of bile salts and nuclear hormone receptors in the regulation of cholesterol homeostasis: bile salts as ligands for nuclear hormone receptors. Can J Gastroenterol 2003;17:265-71
  • Suchy FJ, Ananthanarayanan M. Bile salt excretory pump: biology and pathobiology. J Pediatr Gastroenterol Nutr 2006;43:S10-16
  • Hagenbuch B, Dawson P. The sodium bile salt cotransport family SLC10. Pflügers Archiv 2004;447:566-70
  • Geyer J, Wilke T, Petzinger E. The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships. Naunyn Schmiedebergs Arch Pharmacol 2006;372:413-31
  • Bahar RJ, Stolz A. Bile acid transport. Gastroenterol Clin North Am 1999;28:27-58
  • McClintock C, Shiau Y. Jejunum is more important than terminal ileum for taurocholate absorption in rats. Am J Physiol 1983;244:G507-14
  • Meier PJ, Stieger B. Bile salt transporters. Annu Rev Physiol 2002;64:635-61
  • Falany CN, Johnson MR, Barnes S, et al. Glycine and taurine conjugation of bile acids by a single enzyme. molecular cloning and expression of human liver bile acid CoA:amino acid N-acyltransferase. J Biol Chem 1994;269:19375-9
  • Jansen PL, Groothuis GM, Peters WH, et al. Selective hepatobiliary transport defect for organic anions and neutral steroids in mutant rats with hereditary-conjugated hyperbilirubinemia. Hepatology 1987;7:71-6
  • Ito K, Suzuki H, Hirohashi T, et al. Molecular cloning of canalicular multispecific organic anion transporter defective in EHBR. Am J Physiol-Gastr L 1997;35:G16
  • Takikawa H, Sano N, Narita T, et al. Biliary excretion of bile acid conjugates in a hyperbilirubinemic mutant Sprague-dawley rat. Hepatology 1991;14:352-60
  • Hironaka K, Yasuhito Y, Yukihiro K, et al. Abnormality of oral ursodeoxycholic acid tolerance test in the dubin-johnson syndrome. Clin Chim Acta 1981;112:13-19
  • Kimura A, Ushijima K, Kage M, et al. Neonatal Dubin-Johnson syndrome with severe cholestasis: effective phenobarbital therapy. Acta Paediatrica 1991;80:381-5
  • Shieh CC, Chang MH, Chen CL. Dubin-johnson syndrome presenting with neonatal cholestasis. Arch Dis Child 1990;65:898-9
  • Ogawa K, Suzuki H, Hirohashi T, et al. Characterization of inducible nature of MRP3 in rat liver. Am J Physiol Gastrointest Liver Physiol 2000;278:G438-46
  • Vos TA, Hooiveld GJ, Koning H, et al. Up-regulation of the multidrug resistance genes, Mrp1 and Mdr1b, and down-regulation of the organic anion transporter, Mrp2, and the bile salt transporter, spgp, in endotoxemic rat liver. Hepatology 1998;28:1637-44
  • Jansen PLM, Müller M, Sturm E. Genes and cholestasis. Hepatology 2001;34:1067-74
  • Tanaka Y, Kobayashi Y, Gabazza EC, et al. Increased renal expression of bilirubin glucuronide transporters in a rat model of obstructive jaundice. Am J Physiol Gastrointest Liver Physiol 2002;282:G656-62
  • Kullak-Ublick GA, Stieger B, Hagenbuch B, et al. Hepatic transport of bile salts. Semin Liver Dis 2000;20:273-92
  • Trauner M, Arrese M, Soroka CJ, et al. The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis. Gastroenterology 1997;113:255-64
  • Koopen NR, Wolters H, Havinga R, et al. Impaired activity of the bile canalicular organic anion transporter (MRP2/cmoat) is not the main cause of ethinylestradiol-induced cholestasis in the rat. Hepatology 1998;27:537-45
  • Huang L, Smit JW, Meijer DK, et al. Mrp2 is essential for estradiol‐17β (β‐D‐glucuronide)–induced cholestasis in rats. Hepatology 2000;32:66-72
  • Zimmerman H, Fang M, Utili R, et al. Jaundice due to bacterial infection. Gastroenterology 1979;77:362-74
  • Hinoshita E, Taguchi K, Inokuchi A, et al. Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection. J Hepatol 2001;35:765-73
  • Kalitsky-Szirtes J, Shayeganpour A, Brocks DR, et al. Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metab Dispos 2004;32:20-7
  • Englund G, Jacobson A, Rorsman F, et al. Efflux transporters in ulcerative colitis: decreased expression of BCRP (ABCG2) and Pgp (ABCB1). Inflamm Bowel Dis 2007;13:291-7
  • Petrovic V, Wang JH, Piquette-Miller Effect of endotoxin on the expression of placental drug transporters and glyburide disposition in pregnant rats. Drug Metab Dispos 2008;36:1944-50
  • Nakamura J, Nishida T, Hayashi K, et al. Kupffer cell-mediated down regulation of rat hepatic CMOAT/MRP2 gene expression. Biochem Biophys Res Commun 1999;255:143-9
  • Yoshida S, Ono M, Shono T, et al. Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. Mol Cell Biol 1997;17:4015-23
  • Grilli M, Pizzi M, Memo M, et al. Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation. Science 1996;274:1383-5
  • Polhuijs M, Kuipers F, Vonk RJ, et al. Stereoselectivity of glutathione conjugation: blood elimination of alpha-bromoisovalerylurea enantiomers and biliary excretion of the conjugates in unanesthetized normal or congenitally jaundiced rats. J Pharmacol Exp Ther 1989;249:874-8
  • Hanawa N, Sano N, Takikawa H. Biliary excretion of azelnidipine, a calcium antagonist, in rats. J Gastroenterol Hepatol 2004;19:413-17
  • Jäger W, Gehring E, Hagenauer B, et al. Biliary excretion of flavopiridol and its glucuronides in the isolated perfused rat liver: role of multidrug resistance protein 2 (Mrp2). Life Sci 2003;73:2841-54
  • Takayanagi M, Sano N, Takikawa H. Biliary excretion of olmesartan, an anigotensin II receptor antagonist, in the rat. J Gastroenterol Hepatol 2005;20:784-8
  • Xiong H, Suzuki H, Sugiyama Y, et al. Mechanisms of impaired biliary excretion of acetaminophen glucuronide after acute phenobarbital treatment or phenobarbital pretreatment. Drug Metab Dispos 2002;30:962-9
  • Kuroda M, Kobayashi Y, Tanaka Y, et al. Increased hepatic and renal expressions of multidrug resistance-associated protein 3 in eisai hyperbilirubinuria rats. J Gastroenterol Hepatol 2004;19:146-53
  • Potschka H, Fedrowitz M, Loscher W. Multidrug resistance protein MRP2 contributes to blood-brain barrier function and restricts antiepileptic drug activity. J Pharmacol Exp Ther 2003;306:124-31
  • Potschka H, Fedrowitz M, Löscher W. Brain access and anticonvulsant efficacy of carbamazepine, lamotrigine, and felbamate in ABCC2/MRP2‐Deficient TR− rats. Epilepsia 2003;44:1479-86
  • El-Sheikh AA, Masereeuw R, Russel FG. Mechanisms of renal anionic drug transport. Eur J Pharmacol 2008;585:245-55
  • Chu XY, Strauss JR, Mariano MA, et al. Characterization of mice lacking the multidrug resistance protein MRP2 (ABCC2). J Pharmacol Exp Ther 2006;317:579-89
  • Vlaming ML, Mohrmann K, Wagenaar E, et al. Carcinogen and anticancer drug transport by Mrp2 in vivo: studies using Mrp2 (Abcc2) knockout mice. J Pharmacol Exp Ther 2006;318:319-27
  • Nezasa K, Tian X, Zamek-Gliszczynski MJ, et al. Altered hepatobiliary disposition of 5 (and 6)-carboxy-2’,7’-dichlorofluorescein in Abcg2 (Bcrp1) and Abcc2 (Mrp2) knockout mice. Drug Metab Dispos 2006;34:718-23
  • Lagas JS, Vlaming ML, van Tellingen O, et al. Multidrug resistance protein 2 is an important determinant of paclitaxel pharmacokinetics. Clin Cancer Res 2006;12:6125-32
  • Wang J, Figurski M, Shaw LM, Burckart GJ. The impact of P-glycoprotein and Mrp2 on mycophenolic acid levels in mice. Transpl Immunol 2008;19:192-6
  • Tian X, Li J, Zamek-Gliszczynski MJ, et al. Roles of P-glycoprotein, bcrp, and Mrp2 in biliary excretion of spiramycin in mice. Antimicrob Agents Chemother 2007;51:3230-4
  • Franke R, Lancaster C, Peer C, et al. Effect of ABCC2 (MRP2) transport function on erythromycin metabolism. Clin Pharmacol Ther 2011;89:693-701
  • Green BR, Bain LJ. Mrp2 is involved in the efflux and disposition of fosinopril. J Appl Toxicol 2013;33:458-65
  • Lagas JS, Vlaming ML, Schinkel AH. Pharmacokinetic assessment of multiple ATP-binding cassette transporters: the power of combination knockout mice. Mol Interv 2009;9:136-45
  • Vlaming ML, van Esch A, van de Steeg E, et al. 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 Metab Dispos 2011;39:1338-44
  • van Waterschoot RA, Lagas JS, Wagenaar E, et al. Individual and combined roles of CYP3A, p-glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) in the pharmacokinetics of docetaxel. Int J Cancer 2010;127:2959-64
  • Belinsky MG, Dawson PA, Shchaveleva I, et al. Analysis of the in vivo functions of Mrp3. Mol Pharmacol 2005;68:160-8
  • Zelcer N, Wetering Kvd, Waart RD, et al. Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides. J Hepatol 2006;44:768-75
  • Fernández-Barrena MG, Monte MJ, Latasa MU, et al. Lack of Abcc3 expression impairs bile-acid induced liver growth and delays hepatic regeneration after partial hepatectomy in mice. J Hepatol 2012;56:367-73
  • van de Wetering K, Zelcer N, Kuil A, et al. Multidrug resistance proteins 2 and 3 provide alternative routes for hepatic excretion of morphine-glucuronides. Mol Pharmacol 2007;72:387-94
  • Manautou JE, de Waart DR, Kunne C, et al. Altered disposition of acetaminophen in mice with a disruption of the Mrp3 gene. Hepatology 2005;42:1091-8
  • Kitamura Y, Hirouchi M, Kusuhara H, et al. Increasing systemic exposure of methotrexate by active efflux mediated by multidrug resistance-associated protein 3 (mrp3/abcc3). J Pharmacol Exp Ther 2008;327:465-73
  • Van de Wetering K, Burkon A, Feddema W, et al. Intestinal breast cancer resistance protein (BCRP)/Bcrp1 and multidrug resistance protein 3 (MRP3)/Mrp3 are involved in the pharmacokinetics of resveratrol. Mol Pharmacol 2009;75:876-85
  • Van De Wetering K, Feddema W, Helms JB, et al. Targeted metabolomics identifies glucuronides of dietary phytoestrogens as a major class of MRP3 substrates in vivo. Gastroenterology 2009;137:1725-35
  • Hirouchi M, Kusuhara H, Onuki R, et al. Construction of triple-transfected cells [organic anion-transporting polypeptide (OATP) 1B1/multidrug resistance-associated protein (MRP) 2/MRP3 and OATP1B1/MRP2/MRP4] for analysis of the sinusoidal function of MRP3 and MRP4. Drug Metab Dispos 2009;37:2103-11
  • de Waart DR, Hausler S, Vlaming ML, et al. Hepatic transport mechanisms of cholyl-L-lysyl-fluorescein. J Pharmacol Exp Ther 2010;334:78-86
  • Kitamura Y, Kusuhara H, Sugiyama Y. Basolateral efflux mediated by multidrug resistance-associated protein 3 (Mrp3/Abcc3) facilitates intestinal absorption of folates in mouse. Pharm Res 2010;27:665-72
  • Kitamura Y, Kusuhara H, Sugiyama Y. Functional characterization of multidrug resistance-associated protein 3 (mrp3/abcc3) in the basolateral efflux of glucuronide conjugates in the mouse small intestine. J Pharmacol Exp Ther 2010;332:659-66
  • Vlaming ML, Teunissen SF, van de Steeg E, et al. Bcrp1;Mdr1a/b;Mrp2 combination knockout mice: altered disposition of the dietary carcinogen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and its genotoxic metabolites. Mol Pharmacol 2014;85:520-30
  • de Waart DR, van de Wetering K, Kunne C, et al. Oral availability of cefadroxil depends on ABCC3 and ABCC4. Drug Metabolism and Disposition 2012;40:515-21
  • Vlaming ML, Pala Z, van Esch A, et al. Impact of Abcc2 (Mrp2) and Abcc3 (Mrp3) on the in vivo elimination of methotrexate and its main toxic metabolite 7-hydroxymethotrexate. Clin Cancer Res 2008;14:8152-60
  • Vlaming ML, van Esch A, Pala Z, et al. Abcc2 (Mrp2), Abcc3 (Mrp3), and Abcg2 (Bcrp1) are the main determinants for rapid elimination of methotrexate and its toxic metabolite 7-hydroxymethotrexate in vivo. Mol Cancer Ther 2009;8:3350-9
  • Vlaming ML, Pala Z, van Esch A, et al. Functionally overlapping roles of Abcg2 (Bcrp1) and Abcc2 (Mrp2) in the elimination of methotrexate and its main toxic metabolite 7-hydroxymethotrexate in vivo. Clin Cancer Res 2009;15:3084-93
  • Haenisch S, Zimmermann U, Dazert E, et al. Influence of polymorphisms on ABCB1 and ABCC2 on mRNA and protein expression in normal and cancerous kidney cortex. Pharmacogenomics J 2007;7:56-65
  • Naesens M, Kuypers DR, Verbeke K, et al. Multidrug resistance protein 2 genetic polymorphisms influence mycophenolic acid exposure in renal allograft recipients. Transplantation 2006;82:1074-84
  • Daly AK, Aithal GP, Leathart J, et al. Genetic susceptibility to diclofenac-induced hepatotoxicity: contribution of UGT2B7, CYP2C8, and ABCC2 genotypes. Gastroenterology 2007;132:272-81
  • Qu J, Zhou B, Yin J, et al. ABCC2 polymorphisms and haplotype are associated with drug resistance in chinese epileptic patients. CNS Neurosci Ther 2012;18:647-51
  • Liu Y, Yin Y, Sheng Q, et al. Association of ABCC2 -24C>T polymorphism with high-dose methotrexate plasma concentrations and toxicities in childhood acute lymphoblastic leukemia. PLoS One 2014;9:e82681
  • Miura M, Satoh S, Inoue K, et al. Telmisartan pharmacokinetics in japanese renal transplant recipients. Clin Chim Acta 2009;399:83-7
  • Becker M, Elens L, Visser L, et al. Genetic variation in the ABCC2 gene is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy. Pharmacogenomics J 2011;13:251-6
  • Ranganathan P, Culverhouse R, Marsh S, et al. Methotrexate (MTX) pathway gene polymorphisms and their effects on MTX toxicity in caucasian and african american patients with rheumatoid arthritis. J Rheumatol 2008;35:572-9
  • Stamp LK, Chapman PT, O’Donnell JL, et al. Polymorphisms within the folate pathway predict folate concentrations but are not associated with disease activity in rheumatoid arthritis patients on methotrexate. Pharmacogenet Genomics 2010;20:367-76
  • Lopez-Lopez E, Ballesteros J, Pinan MA, et al. Polymorphisms in the methotrexate transport pathway: a new tool for MTX plasma level prediction in pediatric acute lymphoblastic leukemia. Pharmacogenet Genomics 2013;23:53-61
  • Zgheib NK, Akra-Ismail M, Aridi C, et al. Genetic polymorphisms in candidate genes predict increased toxicity with methotrexate therapy in lebanese children with acute lymphoblastic leukemia. Pharmacogenet Genomics 2014;24:387-96
  • Assaraf YG. The role of multidrug resistance efflux transporters in antifolate resistance and folate homeostasis. Drug Resist Update 2006;9:227-46
  • Kiyotani K, Mushiroda T, Imamura CK, et al. Significant effect of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients. J Clin Oncol 2010;28:1287-93
  • Kauffmann H, Keppler D, Gant TW, et al. Induction of hepatic mrp2 (cmrp/cmoat) gene expression in nonhuman primates treated with rifampicin or tamoxifen. Arch Toxicol 1998;72:763-8
  • Choi HK, Yang JW, Roh SH, et al. Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells. Endocr Relat Cancer 2007;14:293-303
  • Kiyotani K, Mushiroda T, Kubo M, et al. Association of genetic polymorphisms in SLCO1B3 and ABCC2 with docetaxel-induced leukopenia. Cancer Sci 2008;99:967-72
  • Lewis LD, Miller AA, Owzar K, et al. The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia: CALGB 60805 (alliance). Pharmacogenet Genomics 2013;23:29-33
  • Kato K, Kusuhara H, Kumagai Y, et al. Association of multidrug resistance-associated protein 2 single nucleotide polymorphism rs12762549 with the basal plasma levels of phase II metabolites of isoflavonoids in healthy japanese individuals. Pharmacogenet Genomics 2012;22:344-54
  • Wright AW, Dickinson RG. Abolition of valproate-derived choleresis in the Mrp2 transporter-deficient rat. J Pharmacol Exp Ther 2004;310:584-8
  • Dombrowski SM, Desai SY, Marroni M, et al. Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia 2001;42:1501-6
  • Kim WJ, Lee JH, Yi J, et al. A nonsynonymous variation in MRP2/ABCC2 is associated with neurological adverse drug reactions of carbamazepine in patients with epilepsy. Pharmacogenet Genomics 2010;20:249-56
  • Ufer M, von Stulpnagel C, Muhle H, et al. Impact of ABCC2 genotype on antiepileptic drug response in caucasian patients with childhood epilepsy. Pharmacogenet Genomics 2011;21:624-30
  • Grover S, Kukreti R. A systematic review and meta-analysis of the role of ABCC2 variants on drug response in patients with epilepsy. Epilepsia 2013;54:936-45
  • Zou J, Fan H, Chen S, et al. Effect of the ABCC3 -211C/T polymorphism on clopidogrel responsiveness in patients with percutaneous coronary intervention. Clin Exp Pharmacol P 2013;40:504-9
  • Müller PJ, Dally H, Klappenecker CN, et al. Polymorphisms in ABCG2, ABCC3 and CNT1 genes and their possible impact of lung cancer patients. Int J Cancer 2009;124:1669-74
  • Müller P, Asher N, Heled M, et al. Polymorphisms in transporter and phase II metabolism genes as potential modifiers of the predisposition to and treatment outcome of de novo acute myeloid leukemia in israeli ethnic groups. Leuk Res 2008;32:919-29
  • Yee SW, Mefford JA, Singh N, et al. Impact of polymorphisms in drug pathway genes on disease-free survival in adults with acute myeloid leukemia. J Hum Genet 2013;58:353-61
  • de Rotte MC, Bulatovic M, Heijstek MW, et al. ABCB1 and ABCC3 gene polymorphisms are associated with first-year response to methotrexate in juvenile idiopathic arthritis. J Rheumatol 2012;39:2032-40
  • Caronia D, Patino-Garcia A, Peréz-Martínez A, et al. Effect of ABCB1 and ABCC3 polymorphisms on osteosarcoma survival after chemotherapy: a pharmacogenetic study. PLoS One 2011;6:e26091
  • Yang J, Wang Z, Cai H, et al. Effect of variation of ABCB1 and ABCC3 genotypes on the survival of bone tumor cases after chemotherapy. Asian Pac J Cancer Prev 2013;14:4595-8
  • Nagy L, Schwabe JW. Mechanism of the nuclear receptor molecular switch. Trends Biochem Sci 2004;29:317-24
  • Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov 2006;5:993-6
  • Mangelsdorf DJ, Evans RM. The RXR heterodimers and orphan receptors. Cell 1995;83:841-50
  • Chen W, Cai SY, Xu S, et al. Nuclear receptors RXRalpha:RARalpha are repressors for human MRP3 expression. Am J Physiol Gastrointest Liver Physiol 2007;292:G1221-7
  • Moffit JS, Aleksunes LM, Maher JM, et al. Induction of hepatic transporters multidrug resistance-associated proteins (mrp) 3 and 4 by clofibrate is regulated by peroxisome proliferator-activated receptor a. J Pharmacol Exp Ther 2006;317:537-45
  • Qadri I, Iwahashi M, Kullak-Ublick GA, et al. Hepatocyte nuclear factor (HNF) 1 and HNF4 mediate hepatic multidrug resistance protein 2 up-regulation during hepatitis C virus gene expression. Mol Pharmacol 2006;70:627-36
  • Teng S, Jekerle V, Piquette-Miller M. Induction of ABCC3 (MRP3) by pregnane X receptor activators. Drug Metab Dispos 2003;31:1296-9
  • Kast HR, Goodwin B, Tarr PT, et al. Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem 2002;277:2908-15
  • Wada T, Gao J, Xie W. PXR and CAR in energy metabolism. Trends Endocrin Met 2009;20:273-9
  • Hoffart E, Ghebreghiorghis L, Nussler A, et al. Effects of atorvastatin metabolites on induction of drug-metabolizing enzymes and membrane transporters through human pregnane X receptor. Br J Pharmacol 2012;165:1595-608
  • Jones SA, Moore LB, Shenk JL, et al. The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol 2000;14:27-39
  • Teng S, Piquette-Miller M. The involvement of the pregnane X receptor in hepatic gene regulation during inflammation in mice. J Pharmacol Exp Ther 2005;312:841-8
  • Teng S, Piquette-Miller M. Hepatoprotective role of PXR activation and MRP3 in cholic acid-induced cholestasis. Br J Pharmacol 2007;151:367-76
  • Lin JH. Transporter-mediated drug interactions: clinical implications and in vitro assessment. Expert Opin Drug Metab Toxicol 2007;3:81-92
  • Fromm MF, Kauffmann H, Fritz P, et al. The effect of rifampin treatment on intestinal expression of human MRP transporters. Am J Pathol 2000;157:1575-80
  • Jemnitz K, Lengyel G, Vereczkey L. In vitro induction of bilirubin conjugation in primary rat hepatocyte culture. Biochem Biophys Res Commun 2002;291:29-33
  • Lehmann JM, McKee DD, Watson MA, et al. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest 1998;102:1016-23
  • Schuetz EG, Beck WT, Schuetz JD. Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol 1996;49:311-18
  • Niemi M, Backman JT, Fromm MF, et al. Pharmacokinetic interactions with rifampicin. Clin Pharmacokinet 2003;42:819-50
  • Cui Y, König J, Keppler D. Vectorial transport by double-transfected cells expressing the human uptake transporter SLC21A8 and the apical export pump ABCC2. Mol Pharmacol 2001;60:934-43
  • Ellis E, Wagner M, Lammert F, et al. Successful treatment of severe unconjugated hyperbilirubinemia via induction of UGT1A1 by rifampicin. J Hepatol 2006;44:243-5
  • Marschall H, Wagner M, Zollner G, et al. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology 2005;129:476-85
  • Khurana S, Singh P. Rifampin is safe for treatment of pruritus due to chronic cholestasis: A meta‐analysis of prospective randomized-controlled trials. Liver Int 2006;26:943-8
  • Sugatani J, Nishitani S, Yamakawa K, et al. Transcriptional regulation of human UGT1A1 gene expression: Activated glucocorticoid receptor enhances constitutive androstane receptor/pregnane X receptor-mediated UDP-glucuronosyltransferase 1A1 regulation with glucocorticoid receptor-interacting protein 1. Mol Pharmacol 2005;67:845-55
  • Ruiz ML, Villanueva SSM, Luquita MG, et al. Beneficial effect of spironolactone administration on ethynylestradiol-induced cholestasis in the rat: involvement of up-regulation of multidrug resistance-associated protein 2. Drug Metab Dispos 2007;35:2060-6
  • Shelby MK, Klaassen CD. Induction of rat UDP-glucuronosyltransferases in liver and duodenum by microsomal enzyme inducers that activate various transcriptional pathways. Drug Metab Dispos 2006;34:1772-8
  • Chen C, Staudinger JL, Klaassen CD. Nuclear receptor, pregnane X receptor, is required for induction of UDP-glucuronosyltranferases in mouse liver by pregnenolone-16 alpha-carbonitrile. Drug Metab Dispos 2003;31:908-15
  • Hirvioja M, Tuimala R, Vuori J. The treatment of intrahepatic cholestasis of pregnancy by dexamethasone. BJOG-Int J Obstet Gy 1992;99:109-11
  • Kretowicz E, Mclntyre HD. Intrahepatic cholestasis of pregnancy. worsening after dexamethasone.Aust N Z J Obstet Gynaecol 1994;34:211-13
  • Diac M, Kenyon A, Nelson-Piercy C, et al. Dexamethasone in the treatment of obstetric cholestasis: a case series. J Obstet Gynecol 2006;26:110-14
  • Glantz A, Marschall H, Lammert F, et al. Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid. Hepatology 2005;42:1399-405
  • Dussault I, Lin M, Hollister K, et al. Peptide mimeticHIV protease inhibitors are ligands for the orphan receptor S7XR. J Biol Chem 2001;276:33309-12
  • Zhang D, Chando TJ, Everett DW, et al. In vitro inhibition of UDP-glucuronosyltransferases by atazanavir and other HIV protease inhibitors and the relationship of this property to in vivo bilirubin glucuronidation. Drug Metab Dispos 2005;33:1729-39
  • Kliewer SA, Moore JT, Wade L, et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 1998;92:73-82
  • Blumberg B, Sabbagh W, Juguilon H, et al. SXR, a novel steroid and xenobioticsensing nuclear receptor. Genes Dev 1998;12:3195-205
  • Wagner M, Halilbasic E, Marschall H, et al. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. Hepatology 2005;42:420-30
  • Huang W, Zhang J, Moore DD. A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR. J Clin Invest 2004;113:137-43
  • Huang W, Zhang J, Chua SS, et al. Induction of bilirubin clearance by the constitutive androstane receptor (CAR). P Natl Acad Sci USA 2003;100:4156-61
  • Dennery PA. Pharmacological interventions for the treatment of neonatal jaundice. Semin Neonatol 2002;7:111-19
  • Roerig DL, Hasegawa AT, Peterson RE, et al. Effect of chloroquine and phenobarbital on morphine glucuronidation and biliary excretion in the rat. Biochem Pharmacol 1974;23:1331-9
  • Watkins JB, Klaassen CD. Effect of inducers and inhibitors of glucuronidation on the biliary excretion and choleretic action of valproic acid in the rat. J Pharmacol Exp Ther 1982;220:305-10
  • Brouwer KL, Jones JA. Altered hepatobiliary disposition of acetaminophen metabolites after phenobarbital pretreatment and renal ligation: evidence for impaired biliary excretion and a diffusional barrier. J Pharmacol Exp Ther 1990;252:657-64
  • Studenberg SD, Brouwer KL. Impaired biliary excretion of acetaminophen glucuronide in the isolated perfused rat liver after acute phenobarbital treatment and in vivo phenobarbital pretreatment. J Pharmacol Exp Ther 1992;261:1022-7
  • Patel NJ, Zamek-Gliszczynski MJ, Zhang P, et al. Phenobarbital alters hepatic Mrp2 function by direct and indirect interactions. Mol Pharmacol 2003;64:154-9
  • Maher JM, Cheng X, Slitt AL, et al. Induction of the multidrug resistance-associated protein family of transporters by chemical activators of receptor-mediated pathways in mouse liver. Drug Metab Dispos 2005;33:956-62
  • Cherrington NJ, Hartley DP, Li N, et al. Organ distribution of multidrug resistance proteins 1, 2, and 3 (Mrp1, 2, and 3) mRNA and hepatic induction of Mrp3 by constitutive androstane receptor activators in rats. J Pharmacol Exp Ther 2002;300:97-104
  • Demeule M, Brossard M, Turcotte S, et al. Diallyl disulfide, a chemopreventive agent in garlic, induces multidrug resistance-associated protein 2 expression. Biochem Biophys Res Commun 2004;324:937-45
  • Brady JF, Ishizaki H, Fukuto JM, et al. Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites. Chem Res Toxicol 1991;4:642-7
  • Pan J, Hong J, Ma B, et al. Transcriptional activation of cytochrome P450 2B1/2 genes in rat liver by diallyl sulfide, a compound derived from garlic. Arch Biochem Biophys 1993;302:337-42
  • Kostadinova R, Wahli W, Michalik L. PPARs in diseases: control mechanisms of inflammation. Curr Med Chem 2005;12:2995-3009
  • Peters JM, Shah YM, Gonzalez FJ. The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention. Nat Rev Cancer 2012;12:181-95
  • Berger JP, Akiyama TE, Meinke PT. PPARs: therapeutic targets for metabolic disease. Trends Pharmacol Sci 2005;26:244-51
  • Lefebvre P, Chinetti G, Fruchart JC, et al. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. J Clin Invest 2006;116:571-80
  • Honda A, Ikegami T, Nakamuta M, et al. Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. Hepatology 2013;57:1931-41
  • Bigo C, Kaeding J, El Husseini D, et al. PPARα: a master regulator of bilirubin homeostasis. PPAR Res 2014;2014:1-11
  • Johnson DR, Klaassen CD. Regulation of rat multidrug resistance protein 2 by classes of prototypical microsomal enzyme inducers that activate distinct transcription pathways. Toxicol Sci 2002;67:182-9
  • Maher JM, Aleksunes LM, Dieter MZ, et al. Nrf2- and PPAR alpha-mediated regulation of hepatic mrp transporters after exposure to perfluorooctanoic acid and perfluorodecanoic acid. Toxicol Sci 2008;106:319-28
  • de The H, Marchio A, Tiollais P, Dejean A. Differential expression and ligand regulation of the retinoic acid receptor alpha and beta genes. EMBO J 1989;8:429-33
  • Mills Jr OH, Kligman AM. Treatment of acne vulgaris with topically applied erythromycin and tretinoin. Acta Derm Venereol 1978;58:555-7
  • Warrell Jr RP, Frankel SR, Miller Jr WH, et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med 1991;324:1385-93
  • Bissonnette R, Worm M, Gerlach B, et al. Successful retreatment with alitretinoin in patients with relapsed chronic hand eczema. Br J Dermatol 2010;162:420-6
  • Walmsley S, Northfelt DW, Melosky B, et al. Treatment of AIDS-related cutaneous kaposi’s sarcoma with topical alitretinoin (9-cis-retinoic acid) gel. JAIDS J Acquired Immune Defic Syndromes 1999;22:235-46
  • Denson LA, Auld KL, Schiek DS, et al. Interleukin-1beta suppresses retinoid transactivation of two hepatic transporter genes involved in bile formation. J Biol Chem 2000;275:8835-43
  • Mottino AD, Hoffman T, Jennes L, et al. Expression and localization of multidrug resistant protein Mrp2 in rat small intestine. J Pharmacol Exp Ther 2000;293:717-23
  • Berggren S, Gall C, Wollnitz N, et al. Gene and protein expression of P-glycoprotein, MRP1, MRP2, and CYP3A4 in the small and large human intestine. Mol Pharm 2007;4:252-7
  • Kikuchi S, Hata M, Fukumoto K, et al. Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes. Nat Genet 2002;31:320-5
  • Nakano T, Sekine S, Ito K, et al. Ezrin regulates the expression of Mrp2/Abcc2 and Mdr1/Abcb1 along the rat small intestinal tract. Am J Physiol Gastrointest Liver Physiol 2013;305:807-17
  • Sekine S, Ito K, Horie T. Canalicular Mrp2 localization is reversibly regulated by the intracellular redox status. Am J Physiol Gastrointest Liver Physiol 2008;295:1035-41
  • Kudo A, Kashiwagi S, Kajimura M, et al. Kupffer cells alter organic anion transport through multidrug resistance protein 2 in the post–cold ischemic rat liver. Hepatology 2004;39:1099-109
  • Kudo A, Ban D, Aihara A, et al. Decreased Mrp2 transport in severe macrovesicular fatty liver grafts. J Surg Res 2012;178:915-21
  • Maximov PY, Lee TM, Jordan VC. The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice. Curr Clin Pharmacol 2013;8:135-55
  • Balint BL, Nagy L. Selective modulators of PPAR activity as new therapeutic tools in metabolic diseases. Endocr Metab Immune Disord Drug Targets 2006;6:33-43
  • Kamisako T, Leier I, Cui Y, et al. Transport of monoglucuronosyl and bisglucuronosyl bilirubin by recombinant human and rat multidrug resistance protein 2. Hepatology 1999;30:485-90
  • Letschert K, Komatsu M, Hummel-Eisenbeiss J, et al. Vectorial transport of the peptide CCK-8 by double-transfected MDCKII cells stably expressing the organic anion transporter OATP1B3 (OATP8) and the export pump ABCC2. J Pharmacol Exp Ther 2005;313:549-56
  • Ishiguro N, Maeda K, Saito A. Establishment of a set of double transfectants coexpressing organic anion transporting polypeptide 1B3 and hepatic efflux transporters for the characterization of the hepatobiliary transport of telmisartan acylglucuronide. Drug Metab Dispos 2008;36:796-805
  • Kopplow K, Letschert K, Konig J, et al. Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells. Mol Pharmacol 2005;68:1031-8
  • Paulusma C, Geer M, Evers R, et al. Canalicular multispecific organic anion transporter/multidrug resistance protein 2 mediates low-affinity transport of reduced glutathione. Biochem J 1999;338:393-401
  • Evers R, de Haas M, Sparidans R, et al. Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is associated with glutathione export. Br J Cancer 2000;83:375-83
  • Akita H, Suzuki H, Ito K, et al. Characterization of bile acid transport mediated by multidrug resistance associated protein 2 and bile salt export pump. BBA-Biomembranes 2001;1511:7-16
  • Fujiwara K, Shin M, Yoshizaki Y, et al. An in vivo role of Mrp2 in the rat hepatocytes by immunocytochemistry for amoxicillin using the transporter-deficient EHBR. J Mol Histol 2012;43:371-8
  • Sugie M, Asakura E, Zhao YL, et al. Possible involvement of the drug transporters P glycoprotein and multidrug resistance-associated protein Mrp2 in disposition of azithromycin. Antimicrob Agents Chemother 2004;48:809-14
  • Oude Elferink RP, Jansen PL. The role of the canalicular multispecific organic anion transporter in the disposal of endo-and xenobiotics. Pharmacol Ther 1994;64:77-97
  • Kato Y, Takahara S, Kato S, et al. Involvement of multidrug resistance-associated protein 2 (Abcc2) in molecular weight-dependent biliary excretion of beta-lactam antibiotics. Drug Metab Dispos 2008;36:1088-96
  • Ahmed S, Vo NT, Thalhammer T, et al. Involvement of Mrp2 (Abcc2) in biliary excretion of moxifloxacin and its metabolites in the isolated perfused rat liver. J Pharm Pharmacol 2008;60:55-62
  • Koike K, Kawabe T, Tanaka T, et al. A canalicular multispecific organic anion transporter (cMOAT) antisense cDNA enhances drug sensitivity in human hepatic cancer cells. Cancer Res 1997;57:5475-9
  • Kawabe T, Chen Z, Wada M, et al. Enhanced transport of anticancer agents and leukotriene C< sub> 4 by the human canalicular multispecific organic anion transporter (cMOAT/MRP2). FEBS Lett 1999;456:327-31
  • Smitherman PK, Townsend AJ, Kute TE, et al. Role of multidrug resistance protein 2 (MRP2, ABCC2) in alkylating agent detoxification: MRP2 potentiates glutathione S-transferase A1-1-mediated resistance to chlorambucil cytotoxicity. J Pharmacol Exp Ther 2004;308:260-7
  • Huisman MT, Chhatta AA, van Tellingen O, et al. MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid. Int J Cancer 2005;116:824-9
  • Hooijberg JH, Broxterman HJ, Kool M, et al. Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Cancer Res 1999;59:2532-5
  • Chen ZS, Kawabe T, Ono M, et al. Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter. Mol Pharmacol 1999;56:1219-28
  • Evers R, Kool M, van Deemter L, et al. Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA. J Clin Invest 1998;101:1310-19
  • Xiong H, Turner KC, Ward ES, et al. Altered hepatobiliary disposition of acetaminophen glucuronide in isolated perfused livers from multidrug resistance-associated protein 2-deficient TR(-) rats. J Pharmacol Exp Ther 2000;295:512-18
  • Matsushima S, Maeda K, Kondo C, et al. Identification of the hepatic efflux transporters of organic anions using double-transfected madin-darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein. J Pharmacol Exp Ther 2005;314:1059-67
  • Ellis LCJ, Hawksworth GM, Weaver RJ. ATP-dependent transport of statins by human and rat MRP2/Mrp2. Toxicol Appl Pharmacol 2013;269:187-94
  • Seitz S, Kretz-Rommel A, Oude Elferink RP, et al. Selective protein adduct formation of diclofenac glucuronide is critically dependent on the rat canalicular conjugate export pump (Mrp2). Chem Res Toxicol 1998;11:513-19
  • Westley IS, Brogan LR, Morris RG, et al. Role of Mrp2 in the hepatic disposition of mycophenolic acid and its glucuronide metabolites: effects of cyclosporine. Drug Metab Dispos 2006;34:261-6
  • Liu L, Cui Y, Chung AY, et al. Vectorial transport of enalapril by Oatp1a1/Mrp2 and OATP1B1 and OATP1B3/MRP2 in rat and human livers. J Pharmacol Exp Ther 2006;318:395-402
  • Yamada A, Maeda K, Kamiyama E, et al. Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor. Drug Metab Dispos 2007;35:2166-76
  • Yamashiro W, Maeda K, Hirouchi M, et al. Involvement of transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II AT1-receptor, in humans. Drug Metab Dispos 2006;34:1247-54
  • Chu XY, Huskey SE, Braun MP, et al. Transport of ethinylestradiol glucuronide and ethinylestradiol sulfate by the multidrug resistance proteins MRP1, MRP2, and MRP3. J Pharmacol Exp Ther 2004;309:156-64
  • Matsushima S, Maeda K, Hayashi H, et al. Involvement of multiple efflux transporters in hepatic disposition of fexofenadine. Mol Pharmacol 2008;73:1474-83
  • Huisman MT, Smit JW, Crommentuyn KM, et al. Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs. AIDS 2002;16:2295-301
  • Gerk PM, Li W, Megaraj V, et al. Human multidrug resistance protein 2 transports the therapeutic bile salt tauroursodeoxycholate. J Pharmacol Exp Ther 2007;320:893-9
  • Dietrich CG, de Waart DR, Ottenhoff R, et al. Increased bioavailability of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in MRP2-deficient rats. Mol Pharmacol 2001;59:974-80
  • Kala SV, Neely MW, Kala G, et al. The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required for biliary excretion of arsenic. J Biol Chem 2000;275:33404-8
  • Leslie EM, Ito K, Upadhyaya P, et al. Transport of the bèta-O-glucuronide conjugate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by the multidrug resistance protein 1 (MRP1). requirement for glutathione or a non-sulfur-containing analog. J Biol Chem 2001;276:27846-54
  • Smeets PH, van Aubel RA, Wouterse AC, et al. Contribution of multidrug resistance protein 2 (MRP2/ABCC2) to the renal excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel PAH transporter. J Am Soc Nephrol 2004;15:2828-35
  • Leier I, Hummel-Eisenbeiss J, Cui Y, et al. ATP-dependent paraaminohippurate transport by apical multidrug resistance protein MRP2. Kidney Int 2000;57:1636-42
  • Lee YA, Cui Y, König J, et al. Identification and functional characterization of the natural variant MRP3-Arg1297His of human multidrug resistance protein 3 (MRP3/ABCC3). Pharmacogenet Genomics 2004;14:213-23
  • Zeng H, Liu G, Rea PA, et al. Transport of amphipathic anions by human multidrug resistance protein 3. Cancer Res 2000;60:4779-84
  • Zeng H, Chen ZS, Belinsky MG, et al. Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res 2001;61:7225-32
  • Zamek-Gliszczynski MJ, Nezasa K, Tian X, et al. Evaluation of the role of multidrug resistance-associated protein (mrp) 3 and Mrp4 in hepatic basolateral excretion of sulfate and glucuronide metabolites of acetaminophen, 4-methylumbelliferone, and harmol in Abcc3-/- and Abcc4-/- mice. J Pharmacol Exp Ther 2006;319:1485-91

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.