Targeting multidrug resistance protein 1 (MRP1, ABCC1): Past, present, and future

Annual Review of Pharmacology and Toxicology

Volumn 54, Issue , 2014, Pages 95-117

  Cole, Susan P C ^a  

^a QUEEN S UNIVERSITY   (Canada)

Author keywords

ABCC1 polymorphisms; Chemosensitization; Drug resistance; Glutathione homeostasis; Leukotriene modifiers; Organic anion transport; Oxidative stress

Indexed keywords

ANION; ANTIBODY; ANTINEOPLASTIC AGENT; GLUTATHIONE; GLUTATHIONE DISULFIDE; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 1; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 2; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 4; PLANT MEDICINAL PRODUCT;

CHEMOPROPHYLAXIS; CHEMOSENSITIZATION; DRUG SAFETY; DRUG TARGETING; GENE EXPRESSION; GENETIC POLYMORPHISM; GENETICS; HUMAN; MODULATION; NONHUMAN; OXIDATIVE STRESS; PHYSIOLOGY; PRIORITY JOURNAL; REVIEW;

ANIMALS; CLINICAL TRIALS AS TOPIC; DISEASE MODELS, ANIMAL; DRUG RESISTANCE, NEOPLASM; GLUTATHIONE; HUMANS; LEUKOTRIENE C4; MOLECULAR TARGETED THERAPY; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; SUBSTRATE SPECIFICITY;

EID: 84888581611     PISSN: 03621642     EISSN: 15454304     Source Type: Book Series    
DOI: 10.1146/annurev-pharmtox-011613-135959     Document Type: Review

References (101)

1. Cole SPC, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, et al. 1992. Overexpression of a transporter gene in a multidrug resistant human lung cancer cell line. Science 258:1650-54
2. Dean M. 2005. The genetics of ATP-binding cassette transporters. Methods Enzymol. 400:409-29
3. Gottesman MM, Ling V. 2006. The molecular basis of multidrug resistance in cancer: the early years of P-glycoprotein research. FEBS Lett. 580:998-1009
4. Amiri-Kordestani L, Basseville A, Kurdziel K, Fojo A, Bates SE. 2012. Targeting MDR in breast and lung cancer: discriminating its importance from the failure of drug resistance reversal studies. Drug Resist. Updates 15:50-61
5. Schafer BC, Gillet JP, Patel C, Baer MR, Bates SE, Gottesman MM. 2012. Drug resistance: still a daunting challenge to the successful treatment of AML. Drug Resist. Updates 15:62-69
6. Yu M, Ocana A, Tannock IF. 2013. Reversal of ATP-binding cassette drug transporter activity to modulate chemoresistance:Why has it failed to provide clinical benefit? Cancer Metastasis Rev. 32:211-27
7. Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, et al. 1998. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc. Natl. Acad. Sci. USA 95:15665-70
8. Slot AJ, Molinski SV, Cole SPC. 2011. Mammalian multidrug resistance proteins (MRPs). Essays Biochem. 50:179-207
9. Sharom FJ. 2011. The P-glycoprotein multidrug transporter. Essays Biochem. 50:161-78
10. Ni Z, Bikadi Z, Rosenberg MF, Mao Q. 2010. Structure and function of the human breast cancer resistance protein (BCRP/ABCG2). Curr. Drug Metab. 11:603-17
11. Zhou SF, Wang LL, Di YM, Xue CC, Duan W, et al. 2008. Substrates and inhibitors of humanmultidrug resistance associated proteins and the implications in drug development. Curr. Med. Chem. 15:1981-2039
12. Keppler D. 2011. Multidrug resistance proteins (MRPs, ABCCs): importance for pathophysiology and drug therapy. Handb. Exp. Pharmacol. 201:299-323
13. Deeley RG, Cole SPC. 2006. Substrate recognition and transport by multidrug resistance protein 1 (ABCC1). FEBS Lett. 580:1103-11
14. Yang Y, Mo W, Zhang JT. 2010. Role of transmembrane segment 5 and extracellular loop 3 in the homodimerization of human ABCC1. Biochemistry 49:10854-61
15. Cole SPC, Deeley RG. 2006. Transport of glutathione and glutathione conjugates by MRP1. Trends Pharmacol. Sci. 27:438-46
16. Brozik A, Hegedus C, Erdei Z, Hegedus T, Ozvegy-Laczka C, et al. 2011. Tyrosine kinase inhibitors as modulators of ATP binding cassette multidrug transporters: substrates, chemosensitizers or inducers of acquired multidrug resistance? Expert Opin. Drug Metab. Toxicol. 7:623-42
17. Pham AN, Wang J, Fang J, Gao X, Zhang Y, et al. 2009. Pharmacogenomics approach reveals MRP1 (ABCC1)-mediated resistance to geldanamycins. Pharm. Res. 26:936-45
18. Abdul-Ghani R, Serra V, Gyorffy B, Jurchott K, Solf A, et al. 2006. The PI3K inhibitor LY294002 blocks drug export from resistant colon carcinoma cells overexpressing MRP1. Oncogene 25:1743-52
19. Wang EJ, Johnson WW. 2003. The farnesyl protein transferase inhibitor lonafarnib (SCH66336) is an inhibitor of multidrug resistance proteins 1 and 2. Chemotherapy 49:303-8
20. Michaelis M, Rothweiler F, Klassert D, von Deimling A, Weber K, et al. 2009. Reversal of Pglycoprotein-mediated multidrug resistance by the murine double minute 2 antagonist nutlin-3. Cancer Res. 69:416-21
21. Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, et al. 2010. Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ. Res. 106:297-306
22. Wittgen HGM, van den Heuvel JJMW, van den Broek PHH, Dinter-Heidorn H, Koenderink JB, Russel FGM. 2011. Cannabinoid type 1 receptor antagonists modulate transport activity of multidrug resistance-associated proteins MRP1, MRP2, MRP3, and MRP4. Drug Metab. Dispos. 39:1294-302
23. Deeley RG, Westlake C, Cole SPC. 2006. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol. Rev. 86:849-99
24. Semsei AF, Erdelyi DJ, Ungvari I, Csagoly E, Hegyi MZ, et al. 2012. ABCC1 polymorphisms in anthracycline-induced cardiotoxicity in childhood acute lymphoblastic leukaemia. Cell Biol. Int. 36:79-86
25. Haber M, Smith J, Bordow SB, Flemming C, Cohn SL, et al. 2006. Association of high level MRP1 expression with poor clinical outcome in a large prospective study of primary neuroblastoma. J. Clin. Oncol. 24:1546-53
26. Pajic M, Murray J, Marshall GM, Cole SPC, Norris MD, Haber M. 2011. ABCC1 G2012T single nucleotide polymorphism is associated with patient outcome in primary neuroblastoma and altered stability of the ABCC1 gene transcript. Pharmacogenet. Genomics 21:270-79
27. Wijnholds J, Evers R, van Leusden MR, Mol CA, Zaman GJ, et al. 1997. Increased sensitivity to anticancer drugs and decreased inflammatory response in mice lacking the multidrug resistance-associated protein. Nat. Med. 3:1275-79
28. Wijnholds J, Scheffer GL, van der Valk M, van der Valk P, Beijnen JH, et al. 1998. Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage. J. Exp. Med. 188:797-808
29. van Tellingen O, Buckle T, Jonker JW, van der Valk MA, Beijnen JH. 2003. P-glycoprotein and Mrp1 collectively protect the bone marrow from vincristine-induced toxicity in vivo. Br. J. Cancer 89:1776-82
30. Kato S, Ito K, Kato Y, Wakayama T, Kubo Y, et al. 2009. Involvement ofmultidrug resistance-associated protein 1 in intestinal toxicity of methotrexate. Pharm. Res. 26:1467-76
31. ten Hove T, Drillenburg P, Wijnholds J, Te Velde AA, van Deventer SJ. 2002. Differential susceptibility of multidrug resistance protein-1 deficient mice to DSSand TNBS-induced colitis. Dig. Dis. Sci. 47:2056-63
32. Jungsuwadee P, Nithipongvanitch R, Chen Y, Oberley TD, Butterfield DA, et al. 2009. Mrp1 localization and function in cardiac mitochondria after doxorubicin. Mol. Pharmacol. 75:1117-26
33. Stride BD, Grant CE, Loe DW, Hipfner DR, Cole SPC, Deeley RG. 1997. Pharmacological characterization of the murine and human orthologs of multidrug resistance protein in transfected human embryonic kidney cells. Mol. Pharmacol. 52:344-53
34. Monks TJ, Lau SS. 1998. The pharmacology and toxicology of polyphenolic-glutathione conjugates. Annu. Rev. Pharmacol. Toxicol. 38:229-55
35. Schultz MJ, Wijnholds J, Peppelenbosch MP, Vervoordeldonk MJ, Speelman P, et al. 2001. Mice lacking the multidrug resistance protein 1 are resistant to Streptococcus pneumoniae-induced pneumonia. J. Immunol. 166:4059-64
36. Renes J, de Vries EE, Hooiveld GJ, Krikken I, Jansen PL, Müller M. 2000. Multidrug resistance protein MRP1 protects against the toxicity of the major lipid peroxidation product 4-hydroxynonenal. Biochem. J. 350(Pt. 2):555-61
37. Rudd LP, Kabler SL, Morrow CS, Townsend AJ. 2011. Enhanced glutathione depletion, protein adduct formation, and cytotoxicity following exposure to 4-hydroxy-2-nonenal (HNE) in cells expressing human multidrug resistance protein-1 (MRP1) together with human glutathione S-transferase-M1 (GSTM1). Chem. Biol. Interact. 194:113-19
38. Mitra P, Oskeritzian CA, Payne SG, Beaven MA, Milstien S, Spiegel S. 2006. Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc. Natl. Acad. Sci. USA 103:16394-99
39. Cartwright TA, Campos CR, Cannon RE, Miller DS. 2013. Mrp1 is essential for sphingolipid signaling to P-glycoprotein in mouse blood-brain and blood-spinal cord barriers. J. Cereb. Blood Flow Metab. 33:381-88
40. Pineiro R, Maffucci T, Falasca M. 2011. The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. Oncogene 30:142-52
41. Sivils JC, Gonzalez I, Bain LJ. 2010. Mice lacking Mrp1 have reduced testicular steroid hormone levels and alterations in steroid biosynthetic enzymes. Gen. Comp. Endocrinol. 167:51-59
42. Létourneau IJ, Bowers RJ, Deeley RG, Cole SPC. 2005. Limited modulation of the transport activity of the human multidrug resistance proteinsMRP1, MRP2 and MRP3 by nicotine glucuronidemetabolites. Toxicol. Lett. 157:9-19
43. Bellarosa C, Bortolussi G, Tiribelli C. 2009. The role of ABC transporters in protecting cells from bilirubin toxicity. Curr. Pharm. Des. 15:2884-92
44. Beedholm-Ebsen R, van de Wetering K, Hardlei T, Nexø E, Borst P, Moestrup SK. 2010. Identification of multidrug resistance protein (MRP1/ABCC1) as a molecular gate for cellular export of cobalamin. Blood 115:1632-39
45. Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. 2009. Glutathione dysregulation and the etiology and progression of human diseases. Biol. Chem. 390:191-214
46. Ballatori N, Krance SM, Marchan R, Hammond CL. 2009. Plasma membrane glutathione transporters and their roles in cell physiology and pathophysiology. Mol. Aspects Med. 30:13-28
47. Cole SPC, Downes HF, Mirski SE, Clements DJ. 1990. Alterations in glutathione and glutathionerelated enzymes in a multidrug resistant small cell lung cancer cell line. Mol. Pharmacol. 37:192-97
48. Lorico A, Rappa G, Finch RA, Yang D, Flavell RA, Sartorelli AC. 1997. Disruption of the murine MRP gene leads to increased sensitivity to etoposide (VP-15) and increased levels of glutathione. Cancer Res. 57:5238-42
49. Brandmann M, Tulpule K, Schmidt MM, Dringen R. 2012. The antiretroviral protease inhibitors indinavir and nelfinavir stimulateMrp1-mediated GSH export from cultured brain astrocytes. J. Neurochem. 120:78-92
50. Leslie EM, Deeley RG, Cole SPC. 2003. Bioflavonoid stimulation of glutathione transport by the 190-kDa multidrug resistance protein 1 (MRP1). Drug Metab. Dispos. 31:11-15
51. Leslie EM, Bowers RJ, Deeley RG, Cole SPC. 2003. Structural requirements for functional interaction of glutathione tripeptide analogs with the human multidrug resistance protein 1 (MRP1). J. Pharmacol. Exp. Ther. 304:643-53
52. Rothnie A, Callaghan R, Deeley RG, Cole SPC. 2006. Role of GSH in estrone sulfate binding and translocation by the multidrug resistance protein 1 (MRP1/ABCC1). J. Biol. Chem. 281:13906-14
53. Ren XQ, Furukawa T, Nakajima Y, Takahashi H, Aoki S, et al. 2005. GSH inhibits trypsinization of the C-terminal half of human MRP1. J. Biol. Chem. 280:6231-37
54. Park HA, Kubicki N, Gnyawali S, Chan YC, Roy S, et al. 2011. Natural vitamin Eα-tocotrienol protects against ischemic stroke by induction of multidrug resistance-associated protein 1. Stroke 42:2308-14
55. Sreekumar PG, Spee C, Ryan SJ, Cole SPC, Kannan R, Hinton DR. 2012. Mechanism of RPE cell death in α-crystallin deficient mice: a novel and critical role for MRP1-mediated GSH efflux. PLoS ONE 7:e33420
56. Mueller CF, Afzal S, Becher UM, Wassmann S, Nickenig G, Wassmann K. 2010. Role of the multidrug resistance protein-1 (MRP1) for endothelial progenitor cell function and survival. J. Mol. Cell. Cardiol. 49:482-89
57. Suryo Rahmanto Y, Kalinowski DS, Lane DJ, Lok HC, Richardson V, Richardson DR. 2012. Nitrogen monoxide (NO) storage and transport by dinitrosyl-dithiol-iron complexes: long-lived NO that is trafficked by interacting proteins. J. Biol. Chem. 287:6960-68
58. Boumendjel A, Baubichon-Cortay H, Trompier D, Perrotton T, Di Pietro A. 2005. Anticancermultidrug resistance mediated by MRP1: recent advances in the discovery of reversal agents. Med. Res. Rev. 25:453-72
59. Xia CQ, Milton MN, Gan LS. 2007. Evaluation of drug-transporter interactions using in vitro and in vivo models. Curr. Drug Metab. 8:341-63
60. Brouwer KLR, Keppler D, Hoffmaster KA, Bow DAJ, Chen Y, et al. (on behalf of the International Transporter Consortium). 2013. In vitro methods to support transporter evaluation in drug discovery and development. Clin. Pharmacol. Ther. 94:95-112
61. Maeno K, Nakajima A, Conseil G, Rothnie A, Deeley RG, Cole SPC. 2009. Molecular basis for reduced estrone sulfate transport and altered modulator sensitivity of TM6 and TM17mutants of MRP1(ABCC1). Drug Metab. Dispos. 37:1411-20
62. Lagas JS, Vlaming ML, Schinkel AH. 2009. Pharmacokinetic assessment of multiple ATP-binding cassette transporters: the power of combination knockout mice. Mol. Interv. 9:136-45
63. Burkhart CA, Watt F, Murray J, Pajic M, Prokvolit A, et al. 2009. Small-molecule multidrug resistanceassociated protein 1 inhibitor Reversan increases the therapeutic index of chemotherapy inmousemodels of neuroblastoma. Cancer Res. 69:6573-80
64. Leier I, Jedlitschky F, Buchholz U, Cole SPC, Deeley RG, Keppler D. 1994. The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. J. Biol. Chem. 269:27807-10
65. Gekeler V, Ise W, Sanders KH, Ulrich WR, Beck J. 1995. The leukotriene LTD4 receptor antagonist MK571 specifically modulates MRP associated multidrug resistance. Biochem. Biophys. Res. Commun. 208:345-52
66. Nagayama S, Chen ZS, Kitazono M, Takebayashi Y, Niwa K, et al. 1998. Increased sensitivity to vincristine of MDR cells by the leukotriene D4 receptor antagonist, ONO-1078. Cancer Lett. 130:175-82
67. Norman BH, Lander PA, Gruber JM, Kroin JS, Cohen JD, et al. 2005. Cyclohexyl-linked tricyclic isoxazoles are potent and selective modulators of the multidrug resistance protein (MRP1). Bioorg. Med. Chem. Lett. 55:5526-30
68. Dantzig AH, Shepard RL, Pratt SE, Tabas LB, Lander PA, et al. 2004. Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP-binding cassette (ABC) drug transporters. Biochem. Pharmacol. 67:1111-21
69. Myette RL, Conseil G, Ebert SP, Wetzel B, Detty MR, Cole SPC. 2013. Chalcogenopyrylium dyes as differential modulators of organic anion transport by multidrug resistance protein 1 (MRP1), MRP2, and MRP4. Drug Metab. Dispos. 41:1231-39
70. Pellicani RZ, Steanachi A, Niso M, Carotti A, Leonetti F, et al. 2012. Potent galloyl-based selective modulators targeting multidrug resistance associate protein 1 and P-glycoprotein. J. Med. Chem. 55:424-36
71. Li Y, Revalde JL, Reid G, Paxton JW. 2010. Interactions of dietary phytochemicals with ABC transporters: possible implications for drug disposition and multidrug resistance in cancer. Drug Metab. Rev. 42:590-611
72. Morris ME, Zhang S. 2006. Flavonoid-drug interactions: effects of flavonoids on ABC transporters. Life Sci. 78:2116-30
73. Yang AK, He SM, Liu L, Liu JP, Wei MQ, Zhou SF. 2010. Herbal interactions with anticancer drugs: mechanistic and clinical considerations. Curr. Med. Chem. 17:1635-78
74. Ritchie TK, Kwon H, Atkins WM. 2011. Conformational analysis of human ATP-binding cassette transporter ABCB1 in lipid nanodiscs and inhibition by the antibodies MRK16 and UIC2. J. Biol. Chem. 286:39489-96
75. Hipfner DR, Almquist KC, Stride BD, Deeley RG, Cole SPC. 1996. Location of a proteasehypersensitive region in the multidrug resistance protein (MRP) by mapping of the epitope of MRPspecific monoclonal antibody QCRL-1. Cancer Res. 56:3307-14
76. Hipfner DR, Mao Q, Qiu W, Leslie EM, Gao M, et al. 1999. Monoclonal antibodies that inhibit the transport function of the 190 kDa multidrug resistance protein, MRP: localization of their epitopes to the nucleotide binding domains of the protein. J. Biol. Chem. 274:15420-26
77. Scheffer GL, Kool M, Heijn M, de Haas M, Pijnenborg AC, et al. 2000. Specific detection of multidrug resistance proteins MRP1, MRP2, MRP3, MRP5, and MDR3P-glycoprote in with a panel ofmonoclonal antibodies. Cancer Res. 60:5269-77
78. Chen Q, Yang Y, Liu Y, Han B, Zhang JT. 2002. Cytoplasmic retraction of the amino terminus of human multidrug resistance protein 1. Biochemistry 41:9052-62
79. Hou XB, Cui L, Riordan JR, Chang XB. 2000. ATP binding to the first nucleotide-binding domain of multidrug resistance protein MRP1 increases binding and hydrolysis of ATP and trapping of ADP at the second domain. J. Biol. Chem. 277:5110-19
80. Iram SH, Cole SPC. 2012. Mutation of Glu521 or Glu535 in cytoplasmic loop 5 causes differential misfolding in multiple domains of multidrug and organic anion transporter MRP1 (ABCC1). J. Biol. Chem. 287:7543-55
81. Crowley E, McDevitt CA, Callaghan R. 2010. Generating inhibitors of P-glycoprotein: where to, now? Methods Mol. Biol. 596:405-32
82. Kroetz DL, Yee SW, Giacomini KM. 2010. The Pharmacogenomics of Membrane Transporters project: research at the interface of genomics and transporter pharmacology. Clin. Pharmacol. Ther. 87:109-16
83. Conseil G, Deeley RG, Cole SPC. 2005. Polymorphisms of MRP1 (ABCC1) and related ATP-dependent drug transporters. Pharmacogenet. Genomics 15:523-33
84. Létourneau IJ, Deeley RG, Cole SPC. 2005. Functional characterization of non-synonymous single nucleotide polymorphisms in the gene encoding humanmultidrug resistance protein 1 (MRP1/ABCC1). Pharmacogenet. Genomics 15:647-57
85. Turk D, Hall MD, Chu BF, Ludwig JA, Fales HM, et al. 2009. Identification of compounds selectively killing multidrug-resistant cancer cells. Cancer Res. 69:8293-301
86. Wu JH, Batist G. 2013. Glutathione and glutathione analogues: therapeutic potentials. Biochim. Biophys. Acta 1830:3350-53
87. Genoux-Bastide E, Lorendeau D, Nicolle E, Yahiaoui S, Magnard S, et al. 2011. Identification of xanthones as selective killers of cancer cells overexpressing the ABC transporter MRP1. Chem. Med. Chem. 6:1478-84
88. Cho S, Lu M, He X, Ee PL, Bhat U, et al. 2011. Notch1 regulates the expression of the multidrug resistance gene ABCC1/MRP1 in cultured cancer cells. Proc. Natl. Acad. Sci. USA 108:20778-83
89. Stewart AJ, Canitrot Y, Baracchini E, Dean NM, Deeley RG, Cole SPC. 1996. Reduction in expression of the multidrug resistance protein, MRP, in human tumor cells by antisense phosphorothioate oligonucleotides. Biochem. Pharmacol. 51:461-69
90. Garbuzenko OB, Saad M, Pozharov VP, Reuhl KR, Mainelis G, Minko T. 2010. Inhibition of lung tumor growth by complex pulmonary delivery of drugs with oligonucleotides as suppressors of cellular resistance. Proc. Natl. Acad. Sci. USA 107:10737-42
91. Castanotto D, Rossi JJ. 2009. The promises and pitfalls of RNA-interference-based therapeutics. Nature 457:426-33
92. Borel F, van Logtenstein R, Koornneef A, Maczuga P, Ritsema T, et al. 2011. In vivo knock-down of multidrug resistance transporters ABCC1 and ABCC2 by AAV-delivered shRNAs and by artificial miRNAs. J. RNAi Gene Silenc. 7:434-42
93. Liang Z, Wu H, Xia J, Li Y, Zhang Y, et al. 2010. Involvement of miR-326 in chemotherapy resistance of breast cancer through modulating expression of multidrug resistance-associated protein 1. Biochem. Pharmacol. 79:817-24
94. Guo L, Liu Y, Bai Y, Sun Y, Xiao F, Guo Y. 2010. Gene expression profiling of drug-resistant small cell lung cancer cells by combining microRNA and cDNA expression analysis. Eur. J. Cancer 46:1692-702
95. El Azreq MA, Naci D, Aoudjit F. 2012. Collagen/β1 integrin signalling up-regulates the ABCC1/MRP-1 transporter in an ERK/MAPK-dependent manner. Mol. Biol. Cell 23:3473-84
96. Weekes MP, Tan SYL, Poole E, Talbot S, Antrobus R, et al. 2013. Latency-associated degradation of the MRP1 drug transporter during latent human cytomegalovirus infection. Science 340:199-202
97. Devi NS, Doble M. 2012. Leukotriene C4 synthase: upcoming drug target for inflammation. Curr. Drug Targets 13:1107-18
98. Loe DW, Oleschuk CJ, Deeley RG, Cole SPC. 2000. Structure-activity studies of verapamil analogs that modulate transport of leukotriene C4 and reduced glutathione by multidrug resistance protein MRP1. Biochem. Biophys. Res. Commun. 275:795-803
99. Hara Y, Sassi Y, Guibert C, Gambaryan N, Dorfmuller P, et al. 2011. Inhibition of MRP4 prevents and reverses pulmonary hypertension in mice. J. Clin. Investig. 121:2888-97
100. Bakos E, Evers R, Sinko E, Varadi A, Borst P, Sarkadi B. 2000. Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol. Pharmacol. 57:760-68
101. Loe DW, Almquist KC, Deeley RG, Cole SPC. 1996. Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles: demonstration of glutathione-dependent vincristine transport. J. Biol. Chem. 271:9675-82