Apical/basolateral surface expression of drug transporters and its role in vectorial drug transport

Pharmaceutical Research

Volumn 22, Issue 10, 2005, Pages 1559-1577

  Ito, Kousei ^a   Suzuki, Hiroshi ^b   Horie, Toshiharu ^a   Sugiyama, Yuichi ^c  

^a CHIBA UNIVERSITY   (Japan)

^b UNIVERSITY OF TOKYO HOSPITAL   (Japan)

^c UNIVERSITY OF TOKYO   (Japan)

Author keywords

Epithelial cells; Sorting; Transporter; Vectorial transport

Indexed keywords

BREAST CANCER RESISTANCE PROTEIN; CARRIER PROTEIN; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN 3; OCTAMER TRANSCRIPTION FACTOR 1; OCTAMER TRANSCRIPTION FACTOR 2; OCTAMER TRANSCRIPTION FACTOR 4; ORGANIC ANION TRANSPORTER 1; ORGANIC ANION TRANSPORTER 2; ORGANIC ANION TRANSPORTER 3; ORGANIC ANION TRANSPORTER 4; ORGANIC ANION TRANSPORTER 5; ORGANIC ANION TRANSPORTING POLYPEPTIDE 8; ORGANIC ANION TRANSPORTING POLYPEPTIDE 9; ORGANIC ANION TRANSPORTING POLYPEPTIDE A; ORGANIC ANION TRANSPORTING POLYPEPTIDE B; ORGANIC ANION TRANSPORTING POLYPEPTIDE C; ORGANIC ANION TRANSPORTING POLYPEPTIDE D; ORGANIC CATION TRANSPORTER; ORGANIC CATION TRANSPORTER 2; ORGANIC CATION TRANSPORTER 3; PEPTIDE TRANSPORTER 1; PEPTIDE TRANSPORTER 2; SODIUM TAUROCHOLATE COTRANSPORTING POLYPEPTIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AMINO ACID SUBSTITUTION; APICAL MEMBRANE; BASOLATERAL MEMBRANE; BLOOD BRAIN BARRIER; BLOOD CEREBROSPINAL FLUID BARRIER; BLOOD PLACENTA BARRIER; BLOOD TESTIS BARRIER; DRUG EXCRETION; DRUG TRANSPORT; DUBIN JOHNSON SYNDROME; GENETIC DISORDER; HOST CELL; HUMAN; INTESTINE EPITHELIUM; INTRAHEPATIC BILE DUCT; KIDNEY EPITHELIUM; LIVER CELL; MOLECULE; NONHUMAN; NUCLEOTIDE SEQUENCE; POLARIZATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN TARGETING; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSCYTOSIS;

ANIMALS; CELL POLARITY; HUMANS; MEMBRANE TRANSPORT PROTEINS; PHARMACOKINETICS; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 25144450046     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-005-6810-2     Document Type: Review

References (203)

1. K. E. Mostov M. Verges Y. Altschuler 2000 Membrane traffic in polarized epithelial cells Curr. Opin. Cell. Biol. 12 483 490
2. D. A. Groneberg F. Doring P. R. Eynott A. Fischer H. Daniel 2001 Intestinal peptide transport: ex vivo uptake studies and localization of peptide carrier PEPT1 Am. J. Physiol. Gastrointest. Liver Physiol. 281 G697 G704
3. +/peptide transporter PepT1 in human intestine: up-regulated expression in the colonic mucosa of patients with short-bowel syndrome Am. J. Clin. Nutr. 75 922 930
4. H. Shen D. E. Smith T. Yang Y. G. Huang J. B. Schnermann F. C. Brosius III 1999 Localization of PEPT1 and PEPT2 proton-coupled oligopeptide transporter mRNA and protein in rat kidney Am. J. Physiol. 276 F658 F665
5. H. Daniel G. Kottra 2004 The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology Pflugers Arch. 447 610 618
6. M. Trauner J. L. Boyer 2003 Bile salt transporters: molecular characterization, function, and regulation Physiol. Rev. 83 633 671
7. B. L. Shneider P. A. Dawson D. M. Christie W. Hardikar M.H. Wong F. J. Suchy 1995 Cloning and molecular characterization of the ontogeny of a rat ileal sodium-dependent bile acid transporter J. Clin. Invest. 95 745 754
8. K. N. Lazaridis P. Tietz T. Wu S. Kip P. A. Dawson N. F. LaRusso 2000 Alternative splicing of the rat sodium/bile acid transporter changes its cellular localization and transport properties Proc. Natl. Acad. Sci. USA 97 11092 11097
9. D. Kobayashi T. Nozawa K. Imai J. I. Nezu A. Tsuji I. Tamai 2003 Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane J. Pharmacol. Exp. Ther. 306 703 708
10. T. Nozawa K. Imai J. Nezu A. Tsuji I. Tamai 2004 Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human J. Pharmacol. Exp. Ther. 308 438 445
11. F. Thiebaut T. Tsuruo H. Hamada M. M. Gottesman I. Pastan M. C. Willingham 1987 Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues Proc. Natl. Acad. Sci. USA 84 7735 7738
12. F. Thiebaut T. Tsuruo H. Hamada M. M. Gottesman I. Pastan M. C. Willingham 1989 Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein J. Histochem. Cytochem. 37 159 164
13. M. F. Fromm H. M. Kauffmann P. Fritz O. Burk H. K. Kroemer R. W. Warzok M. Eichelbaum W. Siegmund D. Schrenk 2000 The effect of rifampin treatment on intestinal expression of human MRP transporters Am. J. Pathol. 157 1575 1580
14. A. D. Mottino T. Hoffman L. Jennes M. Vore 2000 Expression and localization of multidrug resistant protein mrp2 in rat small intestine J. Pharmacol. Exp. Ther. 293 717 723
15. A. D. Mottino T. Hoffman L. Jennes J. Cao M. Vore 2001 Expression of multidrug resistance-associated protein 2 in small intestine from pregnant and postpartum rats Am. J. Physiol.: Gastrointest. Liver Physiol. 280 G1261 G1273
16. M. Maliepaard G. L. Scheffer I. F. Faneyte M. A. van Gastelen A. C. Pijnenborg A. H. Schinkel M. J. van De Vijver R. J. Scheper J. H. Schellens 2002 Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues Cancer Res. 61 3458 3464
17. J. W. Jonker M. Buitelaar E. Wagenaar M. A. Van Der Valk G. L. Scheffer R. J. Scheper T. Plosch F. Kuipers R. P. Elferink H. Rosing J. H. Beijnen A. H. Schinkel 2002 The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria Proc. Natl. Acad. Sci. USA 99 15649 15654
18. C. G. Dietrich A. Geier R. P. Oude Elferink 2003 ABC of oral bioavailability: transporters as gatekeepers in the gut Gut 52 1788 1795
19. L. M. Chan S. Lowes B. H. Hirst 2004 The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability Eur. J. Pharm. Sci. 21 25 51
20. Y. Gotoh H. Suzuki S. Kinoshita T. Hirohashi Y. Kato Y. Sugiyama 2000 Involvement of an organic anion transporter (canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2) in gastrointestinal secretion of glutathione conjugates in rats J. Pharmacol. Exp. Ther. 292 433 439
21. K. C. Peng F. Cluzeaud M. Bens J. P. Van Huyen M. A. Wioland R. Lacave A. Vandewalle 1999 Tissue and cell distribution of the multidrug resistance-associated protein (MRP) in mouse intestine and kidney J. Histochem. Cytochem. 47 757 768
22. D. Rost S. Mahner Y. Sugiyama W. Stremmel 2002 Expression and localization of the multidrug resistance-associated protein 3 in rat small and large intestine Am. J. Physiol. Gastrointest. Liver Physiol. 282 G720 G726
23. T. Shoji H. Suzuki H. Kusuhara Y. Watanabe S. Sakamoto Y. Sugiyama 2001 ATP-dependent transport of organic anions into isolated basolateral membrane vesicles from rat intestine Am. J. Physiol.: Gastrointest. Liver Physiol. 287 G749 G756
24. J. W. Jonker E. Wagenaar C. A. Mol M. Buitelaar H. Koepsell J. W. Smit A. H. Schinkel 2001 Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (Oct1 [Slc22a1]) gene Mol. Cell. Biol. 21 5471 5477
25. R. A. Van Aubel R. Masereeuw F. G. Russel 2000 Molecular pharmacology of renal organic anion transporters Am. J. Physiol. Renal. Physiol. 279 F216 F232
26. S. H. Wright W. H. Dantzler 2004 Molecular and cellular physiology of renal organic cation and anion transport Physiol. Rev. 84 987 1049
27. M. Hosoyamada T. Sekine Y. Kanai H. Endou 1999 Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney Am. J. Physiol. 276 F122 F128
28. H. Motohashi Y. Sakurai H. Saito S. Masuda Y. Urakami M. Goto A. Fukatsu O. Ogawa K. Inui 2002 Gene expression levels and immunolocalization of organic ion transporters in the human kidney J. Am. Soc. Nephrol. 13 866 874
29. R. Kojima T. Sekine M. Kawachi S. H. Cha Y. Suzuki H. Endou 2002 Immunolocalization of multispecific organic anion transporters, OAT1, OAT2, and OAT3, in rat kidney J. Am. Soc. Nephrol. 13 848 857
30. A. Tojo T. Sekine N. Nakajima M. Hosoyamada Y. Kanai K. Kimura H. Endou 1999 Immunohistochemical localization of multispecific renal organic anion transporter 1 in rat kidney J. Am. Soc. Nephrol. 10 464 471
31. S. H. Cha T. Sekine J. I. Fukushima Y. Kanai Y. Kobayashi T. Goya H. Endou 2001 Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney Mol. Pharmacol. 59 1277 1286
32. M. Hasegawa H. Kusuhara D. Sugiyama K. Ito S. Ueda H. Endou Y. Sugiyama 2002 Functional involvement of rat organic anion transporter 3 (rOat3; Slc22a8) in the renal uptake of organic anions J. Pharmacol. Exp. Ther. 300 746 753
33. Y. Urakami M. Okuda S. Masuda H. Saito K. I. Inui 1998 Functional characteristics and membrane localization of rat multispecific organic cation transporters, OCT1 and OCT2, mediating tubular secretion of cationic drugs J. Pharmacol. Exp. Ther. 287 800 805
34. D. Grundemann V. Gorboulev S. Gambaryan M. Veyhl H. Koepsell 1994 Drug excretion mediated by a new prototype of polyspecific transporter Nature 372 549 552
35. M. Sugawara-Yokoo Y. Urakami H. Koyama K. Fujikura S. Masuda H. Saito T. Naruse K. Inui K. Takata 2000 Differential localization of organic cation transporters rOCT1 and rOCT2 in the basolateral membrane of rat kidney proximal tubules Histochem. Cell. Biol. 114 175 180
36. U. Karbach J. Kricke F. Meyer-Wentrup V. Gorboulev C. Volk D. Loffing-Cueni B. Kaissling S. Bachmann H. Koepsell 2000 Localization of organic cation transporters OCT1 and OCT2 in rat kidney Am. J. Physiol. Renal Physiol. 279 F679 F687
37. X. Wu W. Huang M. E. Ganapathy H. Wang R. Kekuda S. J. Conway F. H. Leibach V. Ganapathy 2000 Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney Am. J. Physiol. Renal Physiol. 279 F449 F458
38. K. Lahjouji G. A. Mitchell I. A. Qureshi 2001 Carnitine transport by organic cation transporters and systemic carnitine deficiency Mol. Genet. Metab. 73 287 297
39. J. Nezu I. Tamai A. Oku R. Ohashi H. Yabuuchi N. Hashimoto H. Nikaido Y. Sai A. Koizumi Y. Shoji G. Takada T. Matsuishi M. Yoshino H. Kato T. Ohura G. Tsujimoto J. Hayakawa M. Shimane A. Tsuji 1999 Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter Nat. Genet. 21 91 94
40. R. Ohashi I. Tamai J. Nezu Ji H. Nikaido N. Hashimoto A. Oku Y. Sai M. Shimane A. Tsuji 2001 Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2 Mol. Pharmacol. 59 358 366
41. A. J. Bergwerk X. Shi A. C. Ford N. Kanai E. Jacquemin R. D. Burk S. Bai P. M. Novikoff B. Stieger P. J. Meier V. L. Schuster A. W. Wolkoff 1996 Immunologic distribution of an organic anion transport protein in rat liver and kidney Am. J.Physiol. 271 G231 G238
42. S. Masuda H. Saito H. Nonoguchi K. Tomita K. Inui 1997 mRNA distribution and membrane localization of the OAT-K1 organic anion transporter in rat renal tubules FEBS Lett. 407 127 131
43. L. Li T. K. Lee P. J. Meier N. Ballatori 1998 Identification of glutathione as a driving force and leukotriene C4 as a substrate for oatp1, the hepatic sinusoidal organic solute transporter J. Biol. Chem. 273 16184 16191
44. S. Masuda A. Takeuchi H. Saito Y. Hashimoto K. Inui 1999 Functional analysis of rat renal organic anion transporter OAT-K1: bidirectional methotrexate transport in apical membrane FEBS Lett. 459 128 132
45. R. A. van Aubel P. H. Smeets J. G. Peters R. J. Bindels F. G. Russel 2002 The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP J. Am. Soc. Nephrol. 13 595 603
46. T. P. Schaub J. Kartenbeck J. Konig O. Vogel R. Witzgall W. Kriz D. Keppler 1997 Expression of the conjugate export pump encoded by the mrp2 gene in the apical membrane of kidney proximal tubules J. Am. Soc. Nephrol. 8 1213 1221
47. T. P. Schaub J. Kartenbeck J. Konig H. Spring J. Dorsam G. Staehler S. Storkel W. F. Thon D. Keppler 1999 Expression of the MRP2 gene-encoded conjugate export pump in human kidney proximal tubules and in renal cell carcinoma J. Am. Soc. Nephrol. 10 1159 1169
48. K. N. Faber M. Muller P. L. Jansen 2003 Drug transport proteins in the liver Adv. Drug Deliv. Rev. 55 107 124
49. K. Ogawa H. Suzuki T. Hirohashi T. Ishikawa P. J. Meier K. Hirose T. Akizawa M. Yoshioka Y. Sugiyama 2000 Characterization of inducible nature of MRP3 in rat liver Am. J. Physiol.: Gastrointest. Liver Physiol. 278 G438 G446
50. Q. L. Pei Y. Kobayashi Y. Tanaka Y. Taguchi K. Higuchi M. Kaito N. Ma R. Semba T. Kamisako Y. Adachi 2002 Increased expression of multidrug resistance-associated protein 1 (mrp1) in hepatocyte basolateral membrane and renal tubular epithelia after bile duct ligation in rats Hepatol. Res. 22 58 64
51. T. A. Vos G. J. Hooiveld H. Koning S. Childs D. K. Meijer H. Moshage P. L. Jansen M. Muller 1998 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 28 1637 1644
52. H. Akita H. Suzuki Y. Sugiyama 2001 Sinusoidal efflux of taurocholate is enhanced in Mrp2-deficient rat liver Pharm. Res. 18 1119 1125
53. A. Bohan W. S. Chen L. A. Denson M. A. Held J. L. Boyer 2003 Tumor necrosis factor alpha-dependent up-regulation of Lrh-1 and Mrp3(Abcc3) reduces liver injury in obstructive cholestasis J. Biol. Chem. 278 36688 36698
54. A. H. Schinkel 1998 Pharmacological insights from P-glycoprotein knockout mice Int. J. Clin. Pharmacol. Ther. 36 9 13
55. L. Li P. J. Meier N. Ballatori 2000 Oatp2 mediates bidirectional organic solute transport: a role for intracellular glutathione Mol. Pharmacol. 58 335 340
56. B. Gao B. Stieger B. Noe J. M. Fritschy P. J. Meier 1999 Localization of the organic anion transporting polypeptide 2 (Oatp2) in capillary endothelium and choroid plexus epithelium of rat brain J. Histochem. Cytochem. 47 1255 1264
57. H. C. Cooray C. G. Blackmore L. Maskell M. A. Barrand 2002 Localisation of breast cancer resistance protein in microvessel endothelium of human brain NeuroReport 13 2059 2063
58. B. Sarkadi C. Ozvegy-Laczka K. Nemet A. Varadi 2004 ABCG2-a transporter for all seasons FEBS Lett. 567 116 120
59. S. E. Bates R. Robey K. Miyake K. Rao D. D. Ross T. Litman 2001 The role of half-transporters in multidrug resistance J. Bioenerg. Biomembr. 33 503 511
60. Y. J. Lee H. Kusuhara J. W. Jonker A. H. Schinkel Y. Sugiyama 2005 Investigation of efflux transport of dehydroepiandrosterone sulfate and mitoxantrone at the mouse blood-brain barrier: a minor role of breast cancer resistance protein J. Pharmacol. Exp. Ther. 312 44 52
61. F. Pizzagalli B. Hagenbuch B. Stieger U. Klenk G. Folkers P. J. Meier 2002 Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter Mol. Endocrinol. 16 2283 2296
62. D. Sugiyama H. Kusuhara H. Taniguchi S. Ishikawa Y. Nozaki H. Aburatani Y. Sugiyama 2003 Functional characterization of rat brain-specific organic anion transporter (Oatp14) at the blood-brain barrier: high affinity transporter for thyroxine J. Biol. Chem. 278 43489 43495
63. C. Shu H. Shen N. S. Teuscher P. J. Lorenzi R. F. Keep D. E. Smith 2002 Role of PEPT2 in peptide/mimetic trafficking at the blood-cerebrospinal fluid barrier: studies in rat choroid plexus epithelial cells in primary culture J. Pharmacol. Exp. Ther. 301 820 829
64. Y. Nagata H. Kusuhara H. Endou Y. Sugiyama 2002 Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus Mol. Pharmacol. 61 982 988
65. B. Hagenbuch P. J. Meier 2003 The superfamily of organic anion transporting polypeptides Biochim. Biophys. Acta 1609 1 18
66. V. V. Rao J. L. Dahlheimer M. E. Bardgett A. Z. Snyder R. A. Finch A. C. Sartorelli D. Piwnica-Worms 1999 Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier Proc. Natl. Acad. Sci. USA 96 3900 3905
67. S. Choudhuri N. J. Cherrington N. Li C. D. Klaassen 2003 Constitutive expression of various xenobiotic and endobiotic transporter mRNAs in the choroid plexus of rats Drug Metab. Dispos. 31 1337 1345
68. M. Leggas M. Adachi G. L. Scheffer D. Sun P. Wielinga G. Du K. E. Mercer Y. Zhuang J. C. Panetta B. Johnston R. J. Scheper C. F. Stewart J. D. Schuetz 2004 Mrp4 confers resistance to topotecan and protects the brain from chemotherapy Mol. Cell. Biol. 24 7612 7621
69. L. M. Augustine R. J. Markelewicz K. Boekelheide N. Cherrington 2005 Xenobiotic and endobiotic transporter mRNA expression in the blood-testis barrier Drug Metab. Dispos. 33 182 189
70. J. Wijnholds G. L. Scheffer M. van der Valk P. van der Valk J. H. Beijnen R. J. Scheper P. Borst 1998 Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage J. Exp. Med. 188 797 808
71. J. Bart H. Hollema H. J. Groen E. G. de Vries N. H. Hendrikse D. T. Sleijfer T. D. Wegman W. Vaalburg W.T. van der Graaf 2004 The distribution of drug-efflux pumps, P-gp, BCRP, MRP1 and MRP2, in the normal blood-testis barrier and in primary testicular tumours Eur. J. Cancer 40 2064 2070
72. M. F. Fromm 2004 Importance of P-glycoprotein at blood-tissue barriers Trends Pharmacol. Sci. 25 423 429
73. A. H. Schinkel J. W. Jonker 2003 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview Adv. Drug Deliv. Rev. 55 3 29
74. M. Nagashige F. Ushigome N. Koyabu K. Hirata M. Kawabuchi T. Hirakawa S. Satoh K. Tsukimori H. Nakano T. Uchiumi M. Kuwano H. Ohtani Y. Sawada 2003 Basal membrane localization of MRP1 in human placental trophoblast Placenta 24 951 958
75. D. E. Atkinson S. L. Greenwood C. P. Sibley J. D. Glazier L. J. Fairbairn 2003 Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer Am. J. Physiol., Cell Physiol. 285 C584 C591
76. M. V. St-Pierre M. A. Serrano R. I. Macias U. Dubs M. Hoechli U. Lauper P. J. Meier J. J. Marin 2000 Expression of members of the multidrug resistance protein family in human term placenta Am. J. Physiol., Regul. Integr. Comp. Physiol. 279 R1495 R1503
77. J. W. Jonker J. W. Smit R. F. Brinkhuis M. Maliepaard J. H. Beijnen J. H. Schellens A. H. Schinkel 2000 Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan J. Natl. Cancer Inst. 92 1651 1656
78. O. Emanuelsson G. von Heijne 2001 Prediction of organellar targeting signals Biochim. Biophys. Acta 1541 114 119
79. J. Moroianu. Nuclear import and export pathways. J. Cell Biochem. Suppl. 76-83 (1999).
80. H. R. Pelham 1990 The retention signal for soluble proteins of theendoplasmic reticulum Trends Biochem. Sci. 15 483 486
81. G. A. Kullak-Ublick M. G. Ismair B. Stieger L. Landmann R. Huber F. Pizzagalli K. Fattinger P. J. Meier B. Hagenbuch 2001 Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver Gastroenterology 120 525 533
82. N. Morita H. Kusuhara T. Sekine H. Endou Y. Sugiyama 2001 Functional characterization of rat organic anion transporter 2 in LLC-PK1 cells J. Pharmacol. Exp. Ther. 298 1179 1184
83. G. D. Simonson A. C. Vincent K. J. Roberg Y. Huang V. Iwanij 1994 Molecular cloning and characterization of a novel liver-specific transport protein J. Cell Sci. 107 1065 1072
84. R. Lu N. Kanai Y. Bao A. W. Wolkoff V. L. Schuster 1996 Regulation of renal oatp mRNA expression by testosterone Am. J. Physiol. 270 F332 F337
85. Y. Kato K. Kuge H. Kusuhara P. J. Meier Y. Sugiyama 2002 Gender difference in the urinary excretion of organic anions in rats J. Pharmacol. Exp. Ther. 302 483 489
86. Y. Gotoh Y. Kato B. Stieger P. J. Meier Y. Sugiyama 2002 Gender difference in the Oatp1-mediated tubular reabsorption of estradiol 17beta-d-glucuronide in rats Am. J. Physiol. Endocrinol. Metab. 282 E1245 E1254
87. S. Masuda K. Ibaramoto A. Takeuchi H. Saito Y. Hashimoto K. I. Inui 1999 Cloning and functional characterization of a new multispecific organic anion transporter, OAT-K2, in rat kidney Mol. Pharmacol. 55 743 752
88. H. Saito S. Masuda K. Inui 1996 Cloning and functional characterization of a novel rat organic anion transporter mediating basolateral uptake of methotrexate in the kidney J. Biol. Chem. 271 20719 20725
89. D. L. Roush C. J. Gottardi H. Y. Naim M. G. Roth M. J. Caplan 1998 Tyrosine-based membrane protein sorting signals are differentially interpreted by polarized Madin-Darby canine kidney and LLC-PK1 epithelial cells J. Biol. Chem. 273 226862 26869
90. H. Folsch H. Ohno J. S. Bonifacino I. Mellman 1999 A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells Cell 99 189 198
91. F. A. Crocenzi A. D. Mottino M. G. Roma 2004 Regulation of synthesis and trafficking of canalicular transporters and its alteration in acquired hepatocellular cholestasis. Experimental therapeutic strategies for its prevention Curr. Med. Chem. 11 501 524
92. C. C. Paulusma M. J. Kothe C. T. Bakker P. J. Bosma I. van Bokhoven J. van Marle U. Bolder G. N. Tytgat R. P. Oude Elferink 2000 Zonal down-regulation and redistribution of the multidrug resistance protein 2 during bile duct ligation in rat liver Hepatology 31 684 693
93. D. Rost J. Kartenbeck D. Keppler 1999 Changes in the localization of the rat canalicular conjugate export pump Mrp2in phalloidin-induced cholestasis Hepatology 29 814 821
94. F. Dombrowski R. Kubitz A. Chittattu M. Wettstein N. Saha D. Haussinger 2000 Electron-microscopic demonstration of multidrug resistance protein 2 (Mrp2) retrieval from the canalicular membrane in response to hyperosmolarity and lipopolysaccharide Biochem. J. 348 183 188
95. M. Schmitt R. Kubitz S. Lizun M. Wettstein D. Haussinger 2001 Regulation of the dynamic localization of the rat Bsep gene-encoded bile salt export pump by anisoosmolarity Hepatology 33 509 518
96. R. Kubitz D. D'Urso D. Keppler D. Haussinger 1997 Osmodependent dynamic localization of the multidrug resistance protein 2 in the rat hepatocyte canalicular membrane Gastroenterology 113 1438 1442
97. F. A. Crocenzi A. D. Mottino J. Cao L. M. Veggi E. J. Sanchez Pozzi M. Vore R. Coleman M. G. Roma 2003 Estradiol-17{beta}-d-glucuronide induces endocytic internalization of bsep in the rat Am. J. Physiol.: Gastrointest. Liver Physiol. 285 G449 G459
98. I. D. Roman M. D. Fernandez-Moreno J. A. Fueyo M. G. Roma R. Coleman 2003 Cyclosporin A induced internalization of the bile salt export pump in isolated rat hepatocyte couplets Toxicol. Sci. 71 276 281
99. J. Shoda T. Miura H. Utsunomiya K. Oda M. Yamamoto M. Kano T. Ikegami N. Tanaka H. Akita K. Ito H. Suzuki Y. Sugiyama 2004 Genipin enhances Mrp2 (Abcc2)-mediated bile formation and organic anion transport in rat liver Hepatology 39 167 178
100. O. Kocher N. Comella A. Gilchrist R. Pal K. Tognazzi L. F. Brown J. H. Knoll 1999 PDZK1, a novel PDZ domain-containing protein up-regulated in carcinomas and mapped to chromosome 1q21, interacts with cMOAT (MRP2), the multidrug resistance-associated protein Lab. Invest. 79 1161 1170
101. T. Hegedus T. Sessler R. Scott W. Thelin E. Bakos A. Varadi K. Szabo L. Homolya S. L. Milgram B. Sarkadi 2003 C-terminal phosphorylation of MRP2 modulates its interaction with PDZ proteins Biochem. Biophys. Res. Commun. 302 454 461
102. A. Bretscher D. Chambers R. Nguyen D. Reczek 2000 ERM-Merlin and EBP50 protein families in plasma membrane organization and function Annu. Rev. Cell. Dev. Biol. 16 113 114
103. P. A. Glynne T. J. Evans 2002 Role of the PDZ scaffolding protein in tubule cells in maintenance of polarised function Exp. Nephrol. 10 307 312
104. M. J. Harris M. Kuwano M. Webb P. G. Board 2001 Identification of the apical membrane-targeting signal of the multidrug resistance-associated protein 2 (MRP2/MOAT) J. Biol. Chem. 276 20876 20881
105. A. T. Nies J. Konig Y. Cui M. Brom H. Spring D. Keppler 2002 Structural requirements for the apical sorting of human multidrug resistance protein 2 (ABCC2) Eur. J. Biochem. 269 1866 1876
106. S. B. Fernandez Z. Hollo A. Kern E. Bakos P. A. Fischer P. Borst R. Evers 2002 Role of the N-terminal transmembrane region of the multidrug resistance protein MRP2 in routing to the apical membrane in MDCKII cells J. Biol. Chem. 277 31048 31055
107. T. Konno T. Ebihara K. Hisaeda T. Uchiumi T. Nakamura T. Shirakusa M. Kuwano M. Wada 2003 Identification of domains participating in the substrate specificity and subcellular localization of the multidrug resistance proteins MRP1 and MRP2 J. Biol. Chem. 278 22908 22917
108. O. Kocher R. Pal M. Roberts C. Cirovic A. Gilchrist 2003 Targeted disruption of the PDZK1 gene by homologous recombination Mol. Cell. Biol. 23 1175 1180
109. M. Ikemoto H. Arai D. Feng K. Tanaka J. Aoki N. Dohmae K. Takio H. Adachi M. Tsujimoto K. Inoue 2000 Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I Proc. Natl. Acad. Sci. USA 97 6538 6543
110. S. Kikuchi M. Hata K. Fukumoto Y. Yamane T. Matsui A. Tamura S. Yonemura H. Yamagishi D. Keppler S. Tsukita 2002 Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes Nat. Genet. 31 320 325
111. H. Kojima A. T. Nies J. Konig W. Hagmann H. Spring M. Uemura H. Fukui D. Keppler 2003 Changes in the expression and localization of hepatocellular transporters and radixin in primary biliary cirrhosis J. Hepatol. 39 693 702
112. D. F. Ortiz J. Moseley G. Calderon A. L. Swift S. Li I. M. Arias 2004 Identification of HAX-1 as a protein that binds bile salt export protein and regulates its abundance in the apical membrane of Madin-Darby canine kidney cells J. Biol. Chem. 279 32761 32770
113. R. G. Tirona B. F. Leake G. Merino R. B. Kim 2001 Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans J. Biol. Chem. 276 35669 35675
114. C. Michalski Y. Cui A. T. Nies A. K. Nuessler P. Neuhaus U. M. Zanger K. Klein M. Eichelbaum D. Keppler J. Konig 2002 A naturally occurring mutation in the SLC21A6 gene causing impaired membrane localization of the hepatocyte uptake transporter J. Biol. Chem. 277 43058 43063
115. Y. Nishizato I. Ieiri H. Suzuki M. Kimura K. Kawabata T. Hirota H. Takane S. Irie H. Kusuhara Y. Urasaki A. Urae S. Higuchi K. Otsubo Y. Sugiyama 2003 Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics Clin. Pharmacol. Ther. 73 554 565
116. M. Iwai H. Suzuki I. Ieiri K. Otsubo Y. Sugiyama 2004 Functional analysis of single nucleotide polymorphisms of hepatic organic anion transporter OATP1B1 (OATP-C) Pharmacogenetics 14 749 757
117. T. Nozawa M. Nakajima I. Tamai K. Noda J. Nezu Y. Sai A. Tsuji T. Yokoi 2002 Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis J. Pharmacol. Exp. Ther. 302 804 813
118. M. Niemi E. Schaeffeler T. Lang M. F. Fromm M. Neuvonen C. Kyrklund J. T. Backman R. Kerb M. Schwab P. J. Neuvonen M. Eichelbaum K. T. Kivisto 2004 High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1) Pharmacogenetics 14 429 440
119. C. Kondo H. Suzuki M. Itoda S. Ozawa J. Sawada D. Kobayashi I. Ieiri K. Mine K. Ohtsubo Y. Sugiyama 2004 Functional analysis of SNPs variants of BCRP/ABCG2 Pharm. Res. 21 1895 1903
120. S. Mizuarai N. Aozasa H. Kotani 2004 Single nucleotide polymorphisms result in impaired membrane localization and reduced ATPase activity in multidrug transporter ABCG2 Int. J. Cancer. 109 238 246
121. H. Suzuki Y. Sugiyama 1998 Excretion of GSSG and glutathione conjugates mediated by MRP1 and cMOAT/MRP2 Semin. Liver. Dis. 18 359 376
122. D. Keppler J. Konig 2000 Hepatic secretion of conjugated drugs and endogenous substances Semin. Liver Dis. 20 265 272
123. R. Mor-Cohen A. Zivelin N. Rosenberg M. Shani S. Muallem U. Seligsohn 2001 Identification and functional analysis of two novel mutations in the multidrug resistance protein 2 gene in Israeli patients with Dubin-Johnson syndrome J. Biol. Chem. 276 36923 36930
124. V. Keitel A. T. Nies M. Brom J. Hummel-Eisenbeiss H. Spring D. Keppler 2003 A common Dubin-Johnson syndrome mutation impairs protein maturation and transport activity of MRP2 (ABCC2) Am. J. Physiol.: Gastrointest. Liver. Physiol. 284 G165 G174
125. K. Hashimoto T. Uchiumi T. Konno T. Ebihara T. Nakamura M. Wada S. Sakisaka F. Maniwa T. Amachi K. Ueda M. Kuwano 2002 Trafficking and functional defects by mutations of the ATP-binding domains in MRP2 in patients with Dubin-Johnson syndrome Hepatology 36 1236 1245
126. V. Keitel J. Kartenbeck A. T. Nies H. Spring M. Brom D. Keppler 2000 Impaired protein maturation of the conjugate export pump multidrug resistance protein 2 as a consequence of a deletion mutation in Dubin-Johnson syndrome Hepatology 32 1317 1328
127. H. Suzuki Y. Sugiyama 2002 Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): its impact on drug disposition Adv. Drug Deliv. Rev. 54 1311 1331
128. L. Wang C. J. Soroka J. L. Boyer 2002 The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II J. Clin. Invest. 110 965 972
129. J. R. Plass O. Mol J. Heegsma M. Geuken J. de Bruin G. Elling M. Muller K. N. Faber P. L. Jansen 2004 A progressive familial intrahepatic cholestasis type 2 mutation causes an unstable, temperature-sensitive bile salt export pump J. Hepatol. 40 24 30
130. G. M. Roomans 2003 Pharmacological approaches to correcting the ion transport defect in cystic fibrosis Am. J. Respir. Medicine 2 413 431
131. A. Q. Sun I. Swaby S. Xu F. J. Suchy 2001 Cell-specific basolateral membrane sorting of the human liver Na(+)-dependent bile acid cotransporter Am. J. Physiol.: Gastrointest. Liver Physiol. 280 G1305 G1313
132. +/Taurocholate cotransporting polypeptide in rat liver Gastroenterology 107 1781 1787
133. A. Q. Sun M. Ananthanarayanan C. J. Soroka S. Thevananther B. L. Shneider F. J. Suchy 1998 Sorting of rat liver and ileal sodium-dependent bile acid transporters in polarized epithelial cells Am. J. Physiol. 275 G1045 G1055
134. D. M. Christie P. A. Dawson S. Thevananther B. L. Shneider 1996 Comparative analysis of the ontogeny of a sodium-dependent bile acid transporter in rat kidney and ileum Am. J. Physiol. 271 G377 G385
135. C. Elsing B. A. Fitscher C. Boker W. Kramer S. Stengelin W. Stremmel 1999 Expression of a bile acid transporter in biliary epithelial cells from normal and cholestatic rat livers Eur. J. Med. Res. 4 165 168
136. K. N. Lazaridis L. Pham P. Tietz R. A. Marinelli P. C. deGroen S. Levine P. A. Dawson N. F. LaRusso 1997 Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter J. Clin. Invest. 100 2714 2721
137. +/peptide cotransporters in rat renal brush-border membranes J. Pharmacol. Exp. Ther. 286 1037 1042
138. +/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestineand kidney J. Pharmacol. Exp. Ther. 275 1631 1637
139. +/peptide cotransporter PEPT1: localization of PEPT1 and transport of beta-lactam antibiotics J. Pharmacol. Exp. Ther. 281 1415 1421
140. F. Meyer-Wentrup U. Karbach V. Gorboulev P. Arndt H. Koepsell 1998 Membrane localization of the electrogenic cation transporter rOCT1 in rat liver Biochem. Biophys. Res. Commun. 248 673 678
141. H. Koepsell 1998 Organic cation transporters in intestine, kidney, liver, and brain Annu. Rev. Physiol. 60 243 266
142. D. H. Sweet D. S. Miller J. B. Pritchard 2001 Ventricular choline transport: a role for organic cation transporter 2 expressed in choroid plexus J. Biol. Chem. 276 41611 41619
143. D. H. Sweet D. S. Miller J. B. Pritchard 2000 Basolateral localization of organic cation transporter 2 in intact renal proximal tubules Am. J. Physiol. Renal Physiol. 279 F826 F834
144. A. Enomoto M. Takeda M. Shimoda S. Narikawa Y. Kobayashi T. Yamamoto T. Sekine S. H. Cha T. Niwa H. Endou 2002 Interaction of human organic anion transporters 2 and 4 with organic anion transport inhibitors J. Pharmacol. Exp. Ther. 301 797 802
145. Y. Nagata H. Kusuhara T. Imaoka H. Endou Y. Sugiyama 2004 Involvement of rat organic anion transporter 3 in the uptake of an organic herbicide, 2,4-dichlorophenoxyacetate, by the isolated rat choroid plexus J. Pharm. Sci. 93 2724 2732
146. E. Babu M. Takeda S. Narikawa Y. Kobayashi A. Enomoto A. Tojo S. H. Cha T. Sekine D. Sakthisekaran H. Endou 2002 Role of human organic anion transporter
147. S. Ekaratanawong N. Anzai P. Jutabha H. Miyazaki R. Noshiro M. Takeda Y. Kanai S. Sophasan H. Endou 2004 Human organic anion transporter 4 is a renal apical organic anion/dicarboxylate exchanger in the proximal tubules J. Pharmacol. Sci. 94 297 304
148. U. Eckhardt A. Schroeder B. Stieger M. Hochli L. Landmann R. Tynes P. J. Meier B. Hagenbuch 1999 Polyspecific substrate uptake by the hepatic organic anion transporter Oatp1 in stably transfected CHO cells Am. J. Physiol. 276 G1037 G1042
149. C. Reichel B. Gao J. Van Montfoort V. Cattori C. Rahner B. Hagenbuch B. Stieger T. Kamisako P. J. Meier 1999 Localization and function of the organic anion-transporting polypeptide Oatp2 in rat liver Gastroenterology 117 688 695
150. C. Dubuisson D. Cresteil M. Desrochers D. Decimo M. Hadchouel E. Jacquemin 1996 Ontogenic expression of the Na(+)-independent organic anion transporting polypeptide (oatp) in rat liver and kidney J. Hepatol. 25 932 940
151. E. C. Friesema R. Docter E. P. Moerings B. Stieger B. Hagenbuch P. J. Meier E. P. Krenning G. Hennemann T. J. Visser 1999 Identification of thyroid hormone transporters Biochem. Biophys. Res. Commun. 254 497 501
152. M. Kakyo H. Sakagami T. Nishio D. Nakai R. Nakagomi T. Tokui T. Naitoh S. Matsuno T. Abe H. Yawo 1999 Immunohistochemical distribution and functional characterization of an organic anion transporting polypeptide 2 (oatp2) FEBS Lett. 445 343 346
153. J. Konig Y. Cui A. T. Nies D. Keppler 2000 A novel human organic anion transporting polypeptide localized to the basolateral hepatocyte membrane Am. J. Physiol.: Gastrointest. Liver Physiol. 278 G156 G164
154. Y. Cui J. Konig A. T. Nies M. Pfannschmidt M. Hergt W. W. Franke W. Alt R. Moll D. Keppler 2003 Detection of the human organic anion transporters SLC21A6 (OATP2) and SLC21A8 (OATP8) in liver and hepatocellular carcinoma Lab. Invest. 83 527 538
155. M. Sasaki H. Suzuki K. Ito T. Abe Y. Sugiyama 2002 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. 277 6497 6503
156. H. C. Walters A. L. Craddock H. Fusegawa M. C. Willingham P. A. Dawson 2000 Expression, transport properties, and chromosomal location of organic anion transporter subtype 3 Am. J.Physiol.: Gastrointest. Liver Physiol. 279 G1188 G1200
157. M. G. Ismair B. Stieger V. Cattori B. Hagenbuch M. Fried P. J. Meier G. A. Kullak-Ublick 2001 Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides OATP4 and OATP8 of rat and human liver Gastroenterology 121 1185 1190
158. J. Konig Y. Cui A. T. Nies D. Keppler 2000 Localization and genomic organization of a new hepatocellular organic anion transporting polypeptide J. Biol. Chem. 275 23161 23168
159. T. Abe M. Unno T. Onogawa T. Tokui T. N. Kondo R. Nakagomi H. Adachi K. Fujiwara M. Okabe T. Suzuki K. Nunoki E. Sato M. Kakyo T. Nishio J. Sugita N. Asano M. Tanemoto M. Seki F. Date K. Ono Y. Kondo K. Shiiba M. Suzuki H. Ohtani T. Shimosegawa K. Iinuma H. Nagura S. Ito S. Matsuno 2001 LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers Gastroenterology 120 1689 1699
160. Y. Cui J. Konig D. Keppler 2001 Vectorial transport by double-transfected cells expressing the human uptake transporter SLC21A8 and the apical export pump ABCC2 Mol. Pharmacol. 60 934 943
161. V. Cattori J. E. van Montfoort B. Stieger L. Landmann D. K. Meijer K. H. Winterhalter P. J. Meier B. Hagenbuch 2001 Localization of organic anion transporting polypeptide 4 (Oatp4) in rat liver and comparison of its substrate specificity with Oatp1, Oatp2 and Oatp3 Pflugers Arch. 443 188 195
162. M. Sasaki H. Suzuki J. Aoki K. Ito P. J. Meier Y. Sugiyama 2004 Prediction of in vivo biliary clearance from the in vitro transcellular transport of organic anions across a double-transfected Madin-Darby canine kidney II monolayer expressing both rat organic anion transporting polypeptide 4 and multidrug resistance associated protein 2 Mol. Pharmacol. 66 450 459
163. K. Tohyama H. Kusuhara Y. Sugiyama 2004 Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood-brain barrier Endocrinology 145 4384 4391
164. T. Mikkaichi T. Suzuki T. Onogawa M. Tanemoto H. Mizutamari M. Okada T. Chaki S. Masuda T. Tokui N. Eto M. Abe F. Satoh M. Unno T. Hishinuma K. Inui S. Ito J. Goto T. Abe 2004 Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney Proc. Natl. Acad. Sci. USA 101 3569 3574
165. I. Behrens W. Kamm A. H. Dantzig T. Kissel 2004 Variation of peptide transporter (PepT1 and HPT1) expression in Caco-2 cells as a function of cell origin J. Pharm. Sci. 93 1743 1754
166. C. Cordon-Cardo J. P. O'Brien J. Boccia D. Casals J. R. Bertino M. R. Melamed 1990 Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues J. Histochem. Cytochem. 38 1277 1287
167. M. Horio K. V. Chin S. J. Currier S. Goldenberg C. Williams I. Pastan M. M. Gottesman J. Handler 1989 Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby canine kidney cell epithelia J. Biol. Chem. 264 14880 14884
168. Y. Tanigawara N. Okamura M. Hirai M. Yasuhara K. Ueda N. Kioka T. Komano R. Hori 1992 Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1) J. Pharmacol. Exp. Ther. 263 840 845
169. A. van Helvoort A. J. Smith H. Sprong I. Fritzsche A. H. Schinkel P. Borst G. van Meer 1996 MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine Cell 87 507 517
170. C. L. Cummins L. M. Mangravite L. Z. Benet 2001 Characterizing the expression of CYP3A4 and efflux transporters (P-gp, MRP1, and MRP2) in CYP3A4-transfected Caco-2 cells after induction with sodium butyrate and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate Pharm. Res. 18 1102 1109
171. A. Gigliozzi F. Fraioli P. Sundaram J. Lee A. Mennone D. Alvaro J. L. Boyer 2000 Molecular identification and functional characterization of Mdr1a in rat cholangiocytes Gastroenterology 119 1113 1122
172. E. G. Schuetz K. Yasuda K. Arimori J. D. Schuetz 1998 Human MDR1 and mouse mdr1a P-glycoprotein alter the cellular retention and disposition of erythromycin, but not of retinoic acid or benzo(a)pyrene Arch. Biochem Biophys. 350 340 347
173. J. W. Smit B. Weert A. H. Schinkel D. K. Meijer 1998 Heterologous expression of various P-glycoproteins in polarized epithelial cells induces directional transport of small (type1) and bulky (type 2) cationic drugs J. Pharmacol. Exp. Ther. 286 321 327
174. P. L. Jansen S. S. Strautnieks E. Jacquemin M. Hadchouel E. M. Sokal G. J. Hooiveld J. H. Koning A. De Jager-Krikken F. Kuipers F. Stellaard C. M. Bijleveld A. Gouw H. Van Goor J. Thompson M. Muller 1999 Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis Gastroenterology 117 1370 1379
175. T. Gerloff B. Stieger B. Hagenbuch J. Madon L. Landmann J. Roth A. F. Hofmann P. J. Meier 1998 The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver J. Biol. Chem. 273 10046 10050
176. P. Fickert G. Zollner A. Fuchsbichler C. Stumptner C. Pojer R. Zenz F. Lammert B. Stieger P. J. Meier K. Zatloukal H. Denk M. Trauner 2001 Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver Gastroenterology 121 170 183
177. A. T. Nies G. Jedlitschky J. Konig C. Herold-Mende H. H. Steiner H. P. Schmitt D. Keppler 2004 Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain Neuroscience 129 349 360
178. C. C. Paulusma M. A. van Geer R. Evers M. Heijn R. Ottenhoff P. Borst R. P. Oude Elferink 1999 Canalicular multispecific organic anion transporter/multidrug resistance protein 2 mediates low-affinity transport of reduced glutathione Biochem. J. 338 393 401
179. E. Bakos R. Evers G. Szakacs G. E. Tusnady E. Welker K. Szabo M. de Haas L. van Deemter P. Borst A. Varadi B. Sarkadi 1998 Functional multidrug resistance protein (MRP1) lacking the N-terminal transmembrane domain J. Biol. Chem. 273 32167 32175
180. R. Evers G. J. Zaman L. van Deemter H. Jansen J. Calafat L. C. Oomen R. P. Oude Elferink P. Borst A. H. Schinkel 1996 Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells J. Clin. Invest. 97 1211 1218
181. H. Roelofsen G. J. Hooiveld H. Koning R. Havinga P. L. Jansen M. Muller 1999 Glutathione S-conjugate transport in hepatocytes entering the cell cycle is preserved by a switch in expression from the apical MRP2 to the basolateral MRP1 transporting protein J. Cell Sci. 112 1395 1404
182. J. Wijnholds E. C. deLange G. L. Scheffer D. J. van den Berg C. A. Mol M. van der Valk A. H. Schinkel R. J. Scheper D. D. Breimer P. Borst 2000 Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier J. Clin. Invest. 105 279 285
183. C. C. Paulusma M. Kool P. J. Bosma G. L. Scheffer F. ter Borg R. J. Scheper G. N. Tytgat P. Borst F. Baas R. P. Oude Elferink 1997 A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome Hepatology 25 1539 1542
184. D. Keppler J. Konig 1997 Hepatic canalicular membrane 5: expression and localization of the conjugate export pump encoded by the MRP2 (cMRP/cMOAT) gene in liver FASEB J. 11 509 516
185. R. Evers M. Kool L. van Deemter H. Janssen J. Calafat L. C. Oomen C. C. Paulusma R. P. Oude Elferink F. Baas A.H. Schinkel P. Borst 1998 Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA J.Clin. Invest. 101 1310 1311
186. T. Kawabe Z. S. Chen M. Wada T. Uchiumi M. Ono S. Akiyama M. Kuwano 1999 Enhanced transport of anticancer agents and leukotriene C4 by the human canalicular multispecific organic anion transporter (cMOAT/MRP2) FEBS Lett. 456 327 331
187. M. Buchler J. Konig M. Brom J. Kartenbeck H. Spring T. Horie D. Keppler 1996 cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats J. Biol. Chem. 271 15091 15098
188. J. Konig D. Rost Y. Cui D. Keppler 1999 Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane Hepatology 29 1156 1163
189. G. L. Scheffer M. Kool M. de Haas J. M. de Vree A. C. Pijnenborg D. K. Bosman R. P. Elferink P. van der Valk P. Borst R. J. Scheper 2002 Tissue distribution and induction of human multidrug resistant protein 3 Lab. Invest. 82 193 201
190. M. Kool M. van der Linden M. de Haas G. L. Scheffer J. M. de Vree A. J. Smith G. Jansen G. J. Peters N. Ponne R. J. Scheper R. P. Elferink F. Baas P. Borst 1999 MRP3, an organic anion transporter able to transport anti-cancer drugs Proc. Natl. Acad. Sci. USA 96 6914 6919
191. C. J. Soroka J. M. Lee F. Azzaroli J. L. Boyer 2001 Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver Hepatology 33 783 791
192. M. Rius A. T. Nies J. Hummel-Eisenbeiss G. Jedlitschky D. Keppler 2003 Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane Hepatology 38 374 384
193. J. Wijnholds C. A. Mol L. van Deemter M. de Haas G. L. Scheffer F. Baas J. H. Beijnen R. J. Scheper S. Hatse E. De Clercq J. Balzarini P. Borst 2000 Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs Proc. Natl. Acad. Sci. USA 97 7476 7481
194. G. L. Scheffer X. Hu A. C. Pijnenborg J. Wijnholds A. A. Bergen R. J. Scheper 2002 MRP6 (ABCC6) detection in normal human tissues and tumors Lab. Invest. 82 515 518
195. E. Sinko A. Ilias O. Ujhelly L. Homolya G. L. Scheffer A. A. Bergen B. Sarkadi A. Varadi 2003 Subcellular localization and N-glycosylation of human ABCC6, expressed in MDCKII cells Biochem. Biophys. Res Commun. 308 263 269
196. J. Madon B. Hagenbuch L. Landmann P. J. Meier B. Stieger 2000 Transport function and hepatocellular localization of mrp6 in rat liver Mol. Pharmacol. 57 634 641
197. S. Aust P. Obrist W. Jaeger M. Klimpfinger G. Tucek F. Wrba E. Penner T. Thalhammer 2004 Subcellular localization of the ABCG2 transporter in normal and malignant human gallbladder epithelium Lab. Invest. 84 1024 1036
198. A. E. van Herwaarden J. W. Jonker E. Wagenaar R. F. Brinkhuis J. H. Schellens J. H. Beijnen A. H. Schinkel 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
199. S. Hori S. Ohtsuki M. Tachikawa N. Kimura T. Kondo M. Watanabe E. Nakashima T. Terasaki 2004 Functional expression of rat ABCG2 on the luminal side of brain capillaries and its enhancement by astrocyte-derived soluble factor(s) J. Neurochem. 90 526 536
200. P. Borst R. Evers M. Kool J. Wijnholds 2000 A family of drug transporters: the multidrug resistance-associated proteins J. Natl. Cancer Inst. 92 1295 1302
201. M. Muller P. L. Jansen 1997 Molecular aspects of hepatobiliary transport Am. J. Physiol. 272 G1285 G1303
202. J. W. Jonker A. H. Schinkel 2004 Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3) J. Pharmacol. Exp. Ther. 308 2 9
203. Y. Tanaka A. L. Slitt T. M. Leazer J. M. Maher C. D. Klaassen 2005 Tissue distribution and hormonal regulation of thebreast cancer resistance protein (Bcrp/Abcg2) in rats andmice Biochem. Biophys. Res. Commun. 326 181 187