ABC Family Transporters

  • Xiaodong LiuEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1141)


The transport of specific molecules across lipid membranes is an essential function of all living organisms. The processes are usually mediated by specific transporters. One of the largest transporter families is the ATP-binding cassette (ABC) family. More than 40 ABC transporters have been identified in human, which are divided into 7 subfamilies (ABCA to ABCG) based on their gene structure, amino acid sequence, domain organization, and phylogenetic analysis. Of them, at least 11 ABC transporters including P-glycoprotein (P-GP/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP/ABCG2) are involved in multidrug resistance (MDR) development. These ABC transporters are expressed in various tissues such as the liver, intestine, kidney, and brain, playing important roles in absorption, distribution, and excretion of drugs. Some ABC transporters are also involved in diverse cellular processes such as maintenance of osmotic homeostasis, antigen processing, cell division, immunity, cholesterol, and lipid trafficking. Several human diseases such as cystic fibrosis, sitosterolemia, Tangier disease, intrahepatic cholestasis, and retinal degeneration are associated with mutations in corresponding transporters. This chapter will describe function and expression of several ABC transporters (such as P-GP, BCRP, and MRPs), their substrates and inhibitors, as well as their clinical significance.


Multidrug resistance P-glycoprotein Breast cancer resistance protein Multidrug resistance-associated proteins ABC gene-related disease 



The project was in part supported by the National Natural Science Foundation of China (No. 81872930; 81573490) and “Double First-Class” University project (No. CPU2018GY22).


  1. Agnani D, Acharya P, Martinez E, Tran TT, Abraham F, Tobin F et al (2011) Fitting the elementary rate constants of the P-GP transporter network in the hMDR1-MDCK confluent cell monolayer using a particle swarm algorithm. PLoS One 6:e25086CrossRefPubMedPubMedCentralGoogle Scholar
  2. Ahmed F, Arseni N, Glimm H, Hiddemann W, Buske C, Feuring-Buske M (2008) Constitutive expression of the ATP-binding cassette transporter ABCG2 enhances the growth potential of early human hematopoietic progenitors. Stem Cells 26:810–818CrossRefGoogle Scholar
  3. Akita H, Suzuki H, Sugiyama Y (2001) Sinusoidal efflux of taurocholate is enhanced in Mrp 2-deficient rat liver. Pharm Res 18:1119–1125CrossRefGoogle Scholar
  4. Akita H, Suzuki H, Sugiyama Y (2002) Sinusoidal efflux of taurocholate correlates with the hepatic expression level of Mrp3. Biochem Biophys Res Commun 299:681–687CrossRefGoogle Scholar
  5. Albrecht C, Viturro E (2007) The ABCA subfamily-Gene and protein structures, functions and associated hereditary diseases. Pflug Arch 453:581–589CrossRefGoogle Scholar
  6. Alexiou GA, Goussia A, Voulgaris S, Fotopoulos AD, Fotakopoulos G, Ntoulia A et al (2012) Prognostic significance of MRP5 immunohistochemical expression in glioblastoma. Cancer Chemother Pharmacol 69:1387–1391CrossRefGoogle Scholar
  7. Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R et al (2009) Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 323:1718–1722CrossRefPubMedPubMedCentralGoogle Scholar
  8. Alqawi O, Bates S, Georges E (2004) Arginine482 to threonine mutation in the breast cancer resistance protein ABCG2 inhibits rhodamine 123 transport while increasing binding. Biochem J 382:711–716CrossRefPubMedPubMedCentralGoogle Scholar
  9. Alrefai WA, Gill RK (2007) Bile Acid transporters: structure, function, regulation and pathophysiological implications. Pharm Res 24:1803–1820CrossRefGoogle Scholar
  10. Al-Shawi MK (2011) Catalytic and transport cycles of ABC exporters. Essays Biochem 50:63–83CrossRefGoogle Scholar
  11. Al-Shboul Q, Mahavadi S, Sriwai W, Grider JR, Murthy KS (2013) Differential expression of multidrug resistance protein 5 and phosphodiesterase 5 and regulation of cGMP levels in phasic and tonic smooth muscle. Am J Physiol Gastrointest Liver Physiol 305:G314–G324CrossRefPubMedPubMedCentralGoogle Scholar
  12. Andolfo I, Russo R, Manna F, De Rosa G, Gambale A, Zouwail S et al (2016) Functional characterization of novel ABCB6 mutations and their clinical implications in familial pseudohyperkalemia. Haematologica 101:909–917CrossRefPubMedPubMedCentralGoogle Scholar
  13. Andric SA, Kostic TS, Stojilkovic SS (2006) Contribution of multidrug resistance protein MRP5 in control of cyclic guanosine 5′-monophosphate intracellular signaling in anterior pituitary cells. Endocrinology 147:3435–3445CrossRefGoogle Scholar
  14. Anglicheau D, Pallet N, Rabant M, Marquet P, Cassinat B, Méria P et al (2006) Role of P-glycoprotein in cyclosporine cytotoxicity in the cyclosporine-sirolimus interaction. Kidney Int 70:1019–1025CrossRefGoogle Scholar
  15. Anglicheau D, Thervet E, Etienne I, Hurault De Ligny B, Le Meur Y, Touchard G et al (2004) CYP3A5 and MDR1 genetic polymorphisms and cyclosporine pharmacokinetics after renal transplantation. Clin Pharmacol Ther 75:422–433CrossRefGoogle Scholar
  16. Arana MR, Tocchetti GN, Rigalli JP, Mottino AD, Villanueva SSM (2016) Physiological and pathophysiological factors affecting the expression and activity of the drug transporter MRP2 in intestine. Impact on its function as membrane barrier. Pharmacol Res 109:32–44CrossRefPubMedPubMedCentralGoogle Scholar
  17. Asano T, Takahashi KA, Fujioka M, Inoue S, Okamoto M, Sugioka N et al (2003) ABCB1 C3435T and G2677T/A polymorphism decreased the risk for steroid-induced osteonecrosis of the femoral head after kidney transplantation. Pharmacogenetics 13:675–682CrossRefGoogle Scholar
  18. Aittoniemi J, Fotinou C, Craig TJ, de Wet H, Proks P, Ashcroft FM (2009) SUR1: a unique ATP-binding cassette protein that functions as an ion channel regulator. Philos Trans R Soc Lond B Biol Sci 364:257–267CrossRefGoogle Scholar
  19. Baier LJ, Muller YL, Remedi MS, Traurig M, Piaggi P, Wiessner G et al (2015) ABCC8 R1420H loss-of-function variant in a Southwest American Indian community a:association with increased birth weight and double risk of type 2 diabetes. Diabetes 64:4322–4332CrossRefPubMedPubMedCentralGoogle Scholar
  20. Bandler PE, Westlake CJ, Grant CE, Cole SPC, Deeley RG (2008) Identification of regions required for apical membrane localization of human multidrug resistance protein 2. Mol Pharmacol 74:9–19CrossRefGoogle Scholar
  21. Bardelmeijer HA, Beijnen JH, Brouwer KR, Rosing H, Nooijen WJ, Schellens JH et al (2000) Increased oral bioavailability of paclitaxel by GF120918 in mice through selective modulation of P-glycoprotein. Clin Cancer Res 6:4416–4421PubMedGoogle Scholar
  22. Barnes KM, Dickstein B, Cutler GB Jr, Fojo T, Bates SE (1996) Steroid treatment, accumulation, and antagonism of P-glycoprotein in multidrug resistant cells. Biochemistry 35:4820–4827CrossRefGoogle Scholar
  23. Beesley J, Johnatty SE, Chen X, Spurdle AB, Peterlongo P et al (2011) No evidence for an association between the earwax-associated polymorphism in ABCC11 and breast cancer risk in Caucasian women. Breast Cancer Res Treat 126:235–239CrossRefGoogle Scholar
  24. Beis K (2015) Structural basis for the mechanism of ABC transporters. Biochem Soc Trans 43:889–893CrossRefGoogle Scholar
  25. Belinsky MG, Dawson PA, Shchaveleva I, Bain LJ, Wang R, Ling V et al (2005) Analysis of the in vivo functions of Mrp3. Mol Pharmacol 68:160–168CrossRefGoogle Scholar
  26. Belleville-Rolland T, Sassi Y, Decouture B, Dreano E, Hulot JS, Gaussem P et al (2016) MRP4 (ABCC4) as a potential pharmacologic target for cardiovascular disease. Pharmacol Res 107:381–389CrossRefGoogle Scholar
  27. Benderra Z, Faussat AM, Sayada L, Perrot JY, Tang R, Chaoui D et al (2005) MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia. Clin Cancer Res 11:7764–7772CrossRefGoogle Scholar
  28. Benzimra J, Derhy S, Rosmorduc O, Menu Y, Poupon R, Arrivé L (2013) Hepatobiliary anomalies associated with ABCB4/MDR3 deficiency in adults: a pictorial essay. Insights Imaging 4:331–338CrossRefPubMedPubMedCentralGoogle Scholar
  29. Bera TK, Lee S, Salvatore G, Lee B, Pastan I (2001) MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer. Mol Med 7:509–516CrossRefPubMedPubMedCentralGoogle Scholar
  30. Berger J, Forss-Petter S, Eichler FS (2014) Pathophysiology of X-linked adrenoleukodystrophy. Biochimie 98:135–142CrossRefPubMedPubMedCentralGoogle Scholar
  31. Billat PA, Ossman T, Saint-Marcoux F, Essig M, Rerolle JP, Kamar N et al (2016) Multidrug resistance-associated protein 4 (MRP4) controls ganciclovir intracellular accumulation and contributes to ganciclovir-induced neutropenia in renal transplant patients. Pharmacol Res 111:501–508CrossRefPubMedPubMedCentralGoogle Scholar
  32. Binkhathlan Z, Lavasanifar A (2013) P-glycoprotein inhibition as a therapeutic approach for overcoming multidrug resistance in cancer: Current status and future perspectives. Curr Cancer Drug Targets 13:326–346CrossRefPubMedPubMedCentralGoogle Scholar
  33. Bodo A, Bakos E, Szeri F, Varadi A, Sarkadi B (2003) Differential modulation of the human liver conjugate transporters MRP2 and MRP3 by bile acids and organic anions. J Biol Chem 278:23529–23537CrossRefPubMedPubMedCentralGoogle Scholar
  34. Bojanic DD, Tarr PT, Gale GD, Smith DJ, Bok D, Chen B et al (2010) Differential expression and function of ABCG1 and ABCG4 during development and ageing. J Lipid Res 51:169–181CrossRefPubMedPubMedCentralGoogle Scholar
  35. Bonadia LC, de Lima Marson FA, Ribeiro JD, Paschoal IA, Pereira MC, Ribeiro AF et al (2014) CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease. Gene 540:183–190CrossRefPubMedPubMedCentralGoogle Scholar
  36. Borst P, de Wolf C, van de Wetering K (2007) Multidrug resistance-associated proteins 3, 4, and 5 Pflugers. Arch-Eur J Physiol 453:661–673CrossRefGoogle Scholar
  37. Bouquié R, Deslandes G, Renaud C, Dailly E, Haloun A, Jolliet P (2011) Colchicine-induced rhabdomyolysis in a heart/lung transplant patient with concurrent use of cyclosporin, pravastatin, and azithromycin. J Clin Rheumatol 17:28–30CrossRefGoogle Scholar
  38. Bram E, Ifergan I, Shafran A, Berman B, Ansen G, Assaraf YG (2006) Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol 58:826–834CrossRefGoogle Scholar
  39. Bridges CC, Joshee L, van den Heuvel JJ, Russel FG, Zalups RK (2013) Glutathione status and the renal elimination of inorganic mercury in the Mrp2(−/−) mouse. PLoS One 8:e73559CrossRefPubMedPubMedCentralGoogle Scholar
  40. Bridges CC, Joshee L, Zalups RK (2012) Placental and fetal disposition of mercuric ions in rats exposed to methylmercury: role of Mrp2. Reprod Toxicol 34:628–634CrossRefPubMedPubMedCentralGoogle Scholar
  41. Brinar M, Cukovic-Cavka S, Bozina N, Ravic KG, Markos P, Ladic A et al (2013) MDR1 polymorphisms are associated with inflammatory bowel disease in a cohort of Croatian IBD patients. BMC Gastroenterol 13:57CrossRefPubMedPubMedCentralGoogle Scholar
  42. Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM (1984) Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224:1121–1124CrossRefPubMedPubMedCentralGoogle Scholar
  43. Budulac SE, Postma DS, Hiemstra PS, Kunz LI, Siedlinski M, Smit HA et al (2010) Multidrug resistance-associated protein-1(MRP1) genetic variants, MRP1 protein levels and severity of COPD. Respir Res 11:60CrossRefPubMedPubMedCentralGoogle Scholar
  44. Budulac SE, Postma DS, Hiemstra PS, Lapperre TS, Kunz LI, Vonk JM et al (2012) Multidrug resistance-associated protein 1 and lung function decline with or without long-term corticosteroids treatment in COPD. Eur J Pharmacol 696:136–142CrossRefPubMedPubMedCentralGoogle Scholar
  45. Burke MA, Ardehali H (2007) Mitochondrial ATP-binding cassette proteins. Transl Res 150:73–78CrossRefGoogle Scholar
  46. Calatozzolo C, Gelati M, Ciusani E, Sciacca FL, Pollo B, Cajola L et al (2005) Expression of drug resistance proteins Pgp, MRP1, MRP3, MRP5 and GST-pi in human glioma. J Neuro-Oncol 74:113–121CrossRefGoogle Scholar
  47. Canet MJ, Merrell MD, Hardwick RN, Bataille AM, Campion SN, Ferreira DW et al (2015) Altered regulation of hepatic efflux transporters disrupts acetaminophen disposition in pediatric nonalcoholic steatohepatitis. Drug Metab Dispos 43:829–835CrossRefPubMedPubMedCentralGoogle Scholar
  48. Capparelli E, Rakhmanina N, Mirochnick M (2005) Pharmacotherapy of perinatal perinatal HIV. Semin Fetal Neonatal Med 10:161–175CrossRefGoogle Scholar
  49. Carew MW, Naranmandura H, Shukalek CB, Le XC, Leslie EM (2011) Monomethylarsenic diglutathione transport by the human multidrug resistance protein 1 (MRP1/ABCC1). Drug Metab Dispos 39:2298–2304CrossRefPubMedPubMedCentralGoogle Scholar
  50. Carrière P, Mantha M, Champagne-Paradis S, Jumarie C (2011) Characterization of basolateral-to-apical transepithelial transport of cadmium in intestinal TC7 cell monolayers. Biometals 24:857–874CrossRefPubMedPubMedCentralGoogle Scholar
  51. 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 33:381–388CrossRefPubMedPubMedCentralGoogle Scholar
  52. Chell S, Kaidi A, Williams AC, Paraskeva C (2006) Mediators of PGE2 synthesis and signalling downstream of COX-2 represent potential targets for the prevention/treatment of colorectal cancer. Biochim Biophys Acta 1766:104–119PubMedPubMedCentralGoogle Scholar
  53. Chen ZS, Guo Y, Belinsky MG, Elena Kotova E, Kruh GD (2005) Transport of bile acids, sulfated steroids, estradiol 17-β-d-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol 67:545–557CrossRefPubMedPubMedCentralGoogle Scholar
  54. Chen HH, Kuo MT (2010) Role of glutathione in the regulation of Cisplatin resistance in cancer chemotherapy. Met Based Drugs pii:430939Google Scholar
  55. Chen ZS, Robey RW, Belinsky MG, Shchaveleva I, Ren XQ, Sugimoto Y et al (2003) Transport of methotrexate, methotrexate polyglutamates, and 17β-estradiol 17-(β-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res 63:4048–4054PubMedPubMedCentralGoogle Scholar
  56. Chen Z, Shi T, Zhang L, Zhu P, Deng M, Huang C et al (2016) Mammalian drug efflux transporters the ATP binding cassette (ABC) family in multidrug resistance: a review of the past decade. Cancer Lett 370:153–164CrossRefPubMedPubMedCentralGoogle Scholar
  57. Chen JJ, Sun YL, Tiwari AK, Xiao ZJ, Sodani K, Yang DH et al (2012) PDE5 inhibitors, sildenafil and vardenafil, reverse multidrug resistance by inhibiting the efflux function of multidrug resistance protein 7 (ATP-binding Cassette C10) transporter. Cancer Sci 103:1531–1537CrossRefPubMedPubMedCentralGoogle Scholar
  58. Chen ZS, Tiwari AK (2011) Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases. FEBS J 278:3226–3245CrossRefPubMedPubMedCentralGoogle Scholar
  59. Chen Y, Vasilenko A, Song X, Valanejad L, Verma R, You S et al (2015) Estrogen and estrogen receptor-α-mediated transrepression of bile salt export pump. Mol Endocrinol 29:613–626CrossRefPubMedPubMedCentralGoogle Scholar
  60. Cheng X, Maher J, Chen C, Klaassen CD (2005) Tissue distribution and ontogeny of mouse organic anion transporting polypeptides (Oatps). Drug Metab Dispos 33:1062–1073CrossRefPubMedPubMedCentralGoogle Scholar
  61. Chiaw PK, Eckford PDW, Bear CE (2011) Insights into the mechanisms underlying CFTR channel activity, the molecular basis for cystic fibrosis and strategies for therapy. Essays Biochem 50:233–248CrossRefGoogle Scholar
  62. Claude C, Mougenot N, Bechaux J, Hadri L, Brockschnieder D, Clergue M et al (2015) Inhalable delivery of AAV-based MRP4/ABCC4 silencing RNA prevents monocrotaline-induced pulmonary hypertension. Mol Ther Methods Clin Dev 2:14065CrossRefPubMedPubMedCentralGoogle Scholar
  63. Coelho D, Kim JC, Miousse IR, Fung S, du Moulin M, Buers I et al (2012) Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. Nat Genet 44:1152–1155CrossRefPubMedPubMedCentralGoogle Scholar
  64. Cohen O, Locketz G, Hershko AY, Gorshtein A, Levy Y (2015) Colchicine- clarithromycin-induced rhabdomyolysis in Familial Mediterranean Fever patients under treatment for Helicobacter pylori. Rheumatol Int 35:1937–1941CrossRefPubMedPubMedCentralGoogle Scholar
  65. Cole SP (2014) Multidrug resistance protein 1(MRP1,ABCC1), a “multitasking” ATP-binding cassette (ABC) transporter. J Biol Chem 289:30880–30888CrossRefPubMedPubMedCentralGoogle Scholar
  66. Copsel S, Bruzzone A, May M, Beyrath J, Wargon V, Cany J et al (2014) Multidrug resistance protein 4/ ATP binding cassette transporter 4: a new potential therapeutic target for acute myeloid leukemia. Oncotarget 5:9308–9321CrossRefPubMedPubMedCentralGoogle Scholar
  67. Copsel S, Garcia C, Diez F, Vermeulem M, Baldi A, Bianciotti LG et al (2011) Multidrug resistance protein 4 (MRP4/ABCC4) regulates cAMP cellular levels and controls human leukemia cell proliferation and differentiation. J Biol Chem 286:6979–6988CrossRefPubMedPubMedCentralGoogle Scholar
  68. Cuperus FJ, Claudel T, Gautherot J, Halilbasic E, Trauner M (2014) The role of canalicular ABC transporters in cholestasis. Drug Metab Dispos 42:546–560CrossRefPubMedPubMedCentralGoogle Scholar
  69. Cusatis G, Gregorc V, Li J, Spreafico A, Ingersoll RG, Verweij J et al (2006) Pharmacogenetics of ABCG2 and adverse reactions to gefi tinib. J Natl Cancer Inst 98:1739–1742CrossRefPubMedPubMedCentralGoogle Scholar
  70. Dahan A, Amidon GL (2009) Segmental dependent transport of low permeability compounds along the small intestine due to p-glycoprotein: the role of efflux transport in the oral absorption of BCS class III drugs. Mol Pharm 6:19–28CrossRefPubMedPubMedCentralGoogle Scholar
  71. Dahan A, Sabit H, Amidon GL (2009) Multiple efflux pumps are involved in the transepithelial transport of colchicine: combined effect of P-glycoprotein and multidrug resistance-associated protein 2 leads to decreased intestinal absorption throughout the entire small intestine. Drug Metabo Dispos 37:2028–2036CrossRefGoogle Scholar
  72. Damiani D, Tiribelli M, Calistri E, Geromin A, Chiarvesio A et al (2006) The prognostic value of P-glycoprotein (ABCB) and breast cancer resistance protein (ABCG2) in adults with de novo acute myeloid leukemia with normal karyotype. Haematologica 91:825–828PubMedPubMedCentralGoogle Scholar
  73. Damiani D, Tiribelli M, Geromin A, Michelutti A, Cavallin M, Sperotto A et al (2015) ABCG2 overexpression in patients with acute myeloid leukemia: impact on stem cell transplantation outcome. Am J Hematol 90:784–789CrossRefPubMedPubMedCentralGoogle Scholar
  74. Dantzig AH, Shepard RL, Cao J, Law KL, Ehlhardt WJ, Baughman TM et al (1996) Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res 56:4171–4179PubMedPubMedCentralGoogle Scholar
  75. Dantzig AH, Shepard RL, Law KL, Tabas L, Pratt S, Gillespie JS et al (1999) Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities. J Pharmacol Exp Ther 290:854–862PubMedPubMedCentralGoogle Scholar
  76. Dazert P, Meissner K, Vogelgesang S, Heydrich B, Eckel L, Böhm M et al (2003) Expression and localization of the multidrug resistance protein 5 (MR5/ABCC5), a cellular export pump for cyclic nucleotides, in human heart. Am J Pathol 163:1567–1577CrossRefPubMedPubMedCentralGoogle Scholar
  77. de Vries NA, Zhao J, Kroon E, Buckle T, Beijnen JH, van Tellingen O (2007) P-glycoprotein and breast cancer resistance protein: two dominant transporters working together in limiting the brain penetration of topotecan. Clin Cancer Res 13:6440–6449CrossRefPubMedPubMedCentralGoogle Scholar
  78. Dean M, Rzhetsky A, Allikmets R (2001) The human ATP-binding cassette(ABC) transporter superfamily. Genome Res 11:1156–1166CrossRefGoogle Scholar
  79. De Lannoy IA, Koren G, Klein J, Charuk J, Silverman M (1992) Cyclosporin and quinidine inhibition of renal digoxin excretion: evidence for luminal secretion of digoxin. Am J Phys 263(4 Pt 2):F613–F622Google Scholar
  80. de Jong FA, Scott-Horton TJ, Kroetz DL, McLeod HL, Friberg LE, Mathijssen RH et al (2007) Irinotecan-induced diarrhea: functional significance of the polymorphic ABCC2 transporter protein. Clin Pharmacol Ther 81:42–49CrossRefPubMedPubMedCentralGoogle Scholar
  81. Decouture B, Dreano E, Belleville-Rolland T, Kuci O, Dizier B, Amine Bazaa A et al (2015) Impaired platelet activation and cAMP homeostasis in MRP4-deficient Mice. Blood 126:1823–1830CrossRefPubMedPubMedCentralGoogle Scholar
  82. del Moral RG, Andujar M, Ramírez C, Gómez-Morales M, Masseroli M, Aguilar M et al (1997) Chronic cyclosporin A nephrotoxicity, P-glycoprotein overexpression, and relationships with intrarenal angiotensin II deposits. Am J Pathol 151:1705–1714PubMedPubMedCentralGoogle Scholar
  83. Deme JC, Hancock MA, Xia X, Shintre CA, Plesa M, Kim JC et al (2014) Purification and interaction analyses of two human lysosomal vitamin B12 transporters: LMBD1 and ABCD4. Mol Membr Biol 31:250–261CrossRefPubMedPubMedCentralGoogle Scholar
  84. Diamanti AP, Rosado M, Germano V, Scarsella M, Giorda E, Podestà E et al (2011) Reversion of resistance to immunosuppressive agents in three patients with psoriatic arthritis by cyclosporine A: modulation of P-glycoprotein function. Clin Immunol 138:9–13CrossRefPubMedPubMedCentralGoogle Scholar
  85. Dickens D, Owen A, Alfirevic A, Pirmohamed M (2013) ABCB1 single nucleotide polymorphisms(1236C>T, 2677G>T, and 3435C>T) do not affect transport activity of human P-glycoprotein. Pharmacogenet Genomics 23:314–323CrossRefPubMedPubMedCentralGoogle Scholar
  86. Dietrich CG, Vehr AK, Martin IV, Gaβer N, Rath T, Roeb E et al (2011) Downregulation of breast cancer resistance protein in colon adenomas reduces cellular xenobiotic resistance and leads to accumulation of a food-derived carcinogen. Int J Cancer 129:546–552CrossRefPubMedPubMedCentralGoogle Scholar
  87. Do TM, Noel-Hudson MS, Ribes S, Besengez C, Smirnova M, Cisternino S et al (2012) ABCG2- and ABCG4-mediated efflux of amyloid-β peptide (1-40) at the mouse blood-brain barrier. J Alzheimers Dis 30:155–166CrossRefPubMedPubMedCentralGoogle Scholar
  88. Drach J, Gsur A, Hamilton G, Zhao S, Angerler J, Fiegl M et al (1996) Involvement of P-glycoprotein in the transmembrane transport of interleukin-2 (IL-2), IL-4, and interferon-gamma in normal human T lymphocytes. Blood 88:1747–1175PubMedPubMedCentralGoogle Scholar
  89. Drenberg CD, Hu S, Li L, Buelow DR, Orwick SJ, Gibson AA et al (2016) ABCC4 is a determinant of cytarabine-induced cytotoxicity and myelosuppression. Clin Transl Sci 9:51–59CrossRefPubMedPubMedCentralGoogle Scholar
  90. Drescher S, Schaeffeler E, Hitzl M, Hofmann U, Schwab M, Brinkmann U et al (2002) MDR1 gene polymorphisms and disposition of the P-glycoprotein substrate fexofenadine. Br J Clin Pharmacol 53:526–534CrossRefPubMedPubMedCentralGoogle Scholar
  91. Drozdzik M, Gröer C, Penski J, Lapczuk J, Ostrowski M, Lai Y et al (2014) Protein abundance of clinically relevant multidrug transporters along the entire length of the human intestine. Mol Pharm 11:3547–3555CrossRefPubMedPubMedCentralGoogle Scholar
  92. Dzierlenga AL, Clarke JD, Hargraves TL, Ainslie GR, Vanderah TW, Mary F, Paine MF et al (2015) Mechanistic basis of altered morphine disposition in nonalcoholic steatohepatitis. J Pharmacol Exp Ther 352:462–470CrossRefPubMedPubMedCentralGoogle Scholar
  93. Eckford PD, Sharom FJ (2009) ABC efflux pump-based resistance to chemotherapy drugs. Chem Rev 109:2989–3011CrossRefGoogle Scholar
  94. Emadi A, Gore SD (2010) Arsenic trioxide- An old drug rediscovered. Blood Rev 24:191–199CrossRefPubMedPubMedCentralGoogle Scholar
  95. Engelen M, Kemp S, Poll-The BT (2014) X-linked adrenoleukodystrophy: pathogenesis and treatment. Curr Neurol Neurosci Rep 14:486CrossRefGoogle Scholar
  96. Engström K, Ameer S, Bernaudat L, Drasch G, Baeuml J, Skerfving S et al (2013) Polymorphisms in genes encoding potential mercury transporters and urine mercury concentrations in populations exposed to mercury vapor from gold mining. Environ Health Perspect 121:85–91CrossRefGoogle Scholar
  97. Ernest S, Bello-Reuss E (1999) Secretion of platelet-activating factor is mediated by MDR1 P-glycoprotein in cultured human mesangial cells. J Am Soc Nephrol 10:2306–2313PubMedGoogle Scholar
  98. Eytan GD, Regev R, Assaraf YG (1996) Functional reconstitution of P-glycoprotein reveals an apparent near stoichiometric drug transport to ATP hydrolysis. J Biol Chem 271:3172–3178CrossRefPubMedPubMedCentralGoogle Scholar
  99. Fan Y, Liu XD (2018) Alterations in expression and function of abc family transporters at blood-brain barrier under liver failure and their clinical significances. Pharmaceutics 10:102CrossRefPubMedPubMedCentralGoogle Scholar
  100. Fanen P, Wohlhuter-Haddad A, Hinzpeter A (2014) Genetics of cystic fibrosis: CFTR mutation classifications toward genotype-based CF therapies. Int J Biochem Cell Biol 52:94–102CrossRefPubMedPubMedCentralGoogle Scholar
  101. Fardel O, Jigorel E, Le Vee M, Payen L (2005) Physiological, pharmacological and clinical features of the multidrug resistance protein 2. Biomed Pharmacother 59:104–114CrossRefPubMedPubMedCentralGoogle Scholar
  102. Fatima S, Zhou S, Sorrentino BP (2012) Abcg2 expression marks tissue-specific stem cells in multiple organs in a mouse progeny tracking model. Stem Cells 30:210–221CrossRefPubMedPubMedCentralGoogle Scholar
  103. Fernández-Barrena MG, Monte MJ, Latasa MU, Uriarte I, Vicente E, Haisul CY, HCY C et al (2012) Lack of Abcc3 expression impairs bile-acid induced liver growth and delays hepatic regeneration after partial hepatectomy in mice. J Hepatol 56:367–373CrossRefPubMedPubMedCentralGoogle Scholar
  104. Ferslew BC, Johnston CK, Tsakalozou E, Bridges AS, Paine MF et al (2015) Altered morphine glucuronide and bile acid disposition in patients with non-alcoholic steatohepatitis. Clin Pharmacol Ther 97:419–427CrossRefPubMedPubMedCentralGoogle Scholar
  105. Flanagan SE, Clauin S, Bellanné-Chantelot C, de Lonlay P, Harries LW, Gloyn AL et al (2009) Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat 30:170–180CrossRefPubMedPubMedCentralGoogle Scholar
  106. Fox E, Widemann BC, Pastakia D, Chen CC, Yang SX, Cole D et al (2015) Pharmacokinetic and pharmacodynamic study of tariquidar (XR9576), a P-glycoprotein inhibitor, in combination with doxorubicin, vinorelbine, or docetaxel in children and adolescents with refractory solid tumors. Cancer Chemother Pharmacol 76:1273–1283CrossRefPubMedPubMedCentralGoogle Scholar
  107. Fellay J, Marzolini C, Meaden ER, Back DJ, Buclin T, Chave JP et al (2002) Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 359:30–36CrossRefPubMedPubMedCentralGoogle Scholar
  108. Filipits M, Pohl G, Rudas M, Dietze O, Lax S, Grill R et al (2005) Clinical role of multidrug resistance protein 1 expression in chemotherapy resistance in early-stage breast cancer: the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 23:1161–1168CrossRefPubMedPubMedCentralGoogle Scholar
  109. Frank MH, Denton MD, Alexander SI, Khoury SJ, Sayegh MH, Briscoe DM (2001) Specific MDR1 P-glycoprotein blockade inhibits human alloimmune T cell activation in vitro. J Immunol 166:2451–2459CrossRefPubMedPubMedCentralGoogle Scholar
  110. Fricker G, Drewe J, Huwyler J, Gutmann H, Beglinger C (1996) Relevance of p-glycoprotein for the enteral absorption of cyclosporin A: in vitro-in vivo correlation. Br J Pharmacol 118:1841–1847CrossRefPubMedPubMedCentralGoogle Scholar
  111. Fu Y, Hsiao JH, Paxinos G, Halliday GM, Kim WS (2015) ABCA5 regulates amyloid-β peptide production and is associated with Alzheimer’s disease neuropathology. J Alzheimers Dis 43:857–869CrossRefPubMedPubMedCentralGoogle Scholar
  112. Fukuda Y, Cheong PL, Lynch J, Brighton C, Frase S, Kargas V et al (2016) The severity of hereditary porphyria is modulated by the porphyrin exporter and Lan antigen ABCB6. Nat Commun 7:12353CrossRefPubMedPubMedCentralGoogle Scholar
  113. Fukuda Y, Takenaka K, Sparreboom A, Cheepala SB, Wu CP, Sean Ekins S et al (2013) Human immunodeficiency virus protease inhibitors interact with ATP binding cassette transporter 4/multidrug resistance protein 4: a basis for unanticipated enhanced cytotoxicity. Mol Pharmacol 84:361–371CrossRefPubMedPubMedCentralGoogle Scholar
  114. Fung KL, Gottesman MM (2009) A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function. Biochim Biophys Acta 1794:860–871CrossRefPubMedPubMedCentralGoogle Scholar
  115. Gadsby DC, Vergani P, Csanady L (2006) The ABC protein turned chloride channel whose failure causes cystic fibrosis. Nature 440:477–483CrossRefPubMedPubMedCentralGoogle Scholar
  116. Gazzaniga P, Gradilone A, Petracca A, Nicolazzo C, C Raimondi C, Iacovelli R et al (2010) Molecular markers in circulating tumour cells from metastatic colorectal cancer patients. J Cel Mol Med 14:2073–2077CrossRefGoogle Scholar
  117. George AM, Jones PM (2012) Perspectives on the structure-function of ABC transporters: the Switch and Constant Contact models. Prog Biophys Mol Biol 109:95–107CrossRefPubMedPubMedCentralGoogle Scholar
  118. Gerloff T, Schaefer M, Johne A, Oselin K, Meisel C, Cascorbi I et al (2002) MDR1 genotypes do not influence the absorption of a single oral dose of 1 mg digoxin inhealthy white males. Br J Clin Pharmacol 54:610–616CrossRefPubMedPubMedCentralGoogle Scholar
  119. Geyer J, Gavrilova O, Petzinger E (2009) Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. J Vet Pharmacol Ther 32:87–96CrossRefGoogle Scholar
  120. Ghafouri H, Ghaderi B, Amini S, Nikkhoo B, Abdi M, Hoseini A (2016) Association of ABCB1 and ABCG2 single nucleotide polymorphisms with clinical findings and response to chemotherapy treatments in Kurdish patients with breast cancer. Tumor Biol 37:7901–7906CrossRefGoogle Scholar
  121. Glover JA, Hughes CM, Cantwell MM, Murray LJ (2011) A systematic review to establish the frequency of cyclooxygenase-2 expression in normal breast epithelium, ductal carcinoma in situ, microinvasive carcinoma of the breast and invasive breast cancer. Br J Cancer 105:13–17CrossRefPubMedPubMedCentralGoogle Scholar
  122. Gomes T, Mamdani MM, Juurlink DN (2009) Macrolide-induced digoxin toxicity: a population-based study. Clin Pharmacol Ther 86:383–386CrossRefPubMedPubMedCentralGoogle Scholar
  123. Grant CE, Gao M, DeGorter MK, Cole SP, Deeley RG (2008) Structural determinants of substrate specificity differences between human multidrug resistance protein (MRP) 1 (ABCC1) and MRP3(ABCC3). Drug Metab Dispos 36:2571–2581CrossRefPubMedPubMedCentralGoogle Scholar
  124. Greenhough A, Smartt HJM, Moore AE, Roberts HR, Williams AC, Paraskeva C et al (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcino- genesis 30:377–386CrossRefGoogle Scholar
  125. Guo Y, Kock K, Ritter CA, Chen ZS, Grube M, Jedlitschky G et al (2009) Expression of ABCC-type nucleotide exporters in blasts of adult acute myeloid leukemia: relation to long-term survival. Clin Cancer Res 15:1762–1769CrossRefPubMedPubMedCentralGoogle Scholar
  126. Guo Y, Kotova E, Chen ZS, Lee K, Hopper-Borge E, Belinsky MG et al (2003) MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2′,3′-dideoxycytidine and 9′-(2′-phosphonylmethoxyethyl) adenine. J Biol Chem 278:29509–29514CrossRefPubMedPubMedCentralGoogle Scholar
  127. Gupta N, Martin PM, Miyauchi S, Ananth S, Herdman AV, Martindale RG et al (2006) Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer. Biochem Biophys Res Commun 343:571–577CrossRefPubMedPubMedCentralGoogle Scholar
  128. Gupta A, Zhang Y, Unadkat JD, Mao Q (2004) HIV protease inhibitors are nhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther 310:334–341CrossRefPubMedPubMedCentralGoogle Scholar
  129. Haber M, Smith J, Bordow SB, Flemming C, Cohn SL, London WB et al (2006) Association of high-level MRP1 expression with poor clinical outcome in a large prospective study of primary neuroblastoma. J Clin Oncol 24:1546–1553CrossRefPubMedPubMedCentralGoogle Scholar
  130. Haghverdizadeh P, Haerian MS, Haghverdizadeh P, Haerian BS (2014) ABCC8 genetic variants and risk of diabetes mellitus. Gene 545:198–204CrossRefPubMedPubMedCentralGoogle Scholar
  131. Halon A, Materna V, Donizy P, Matkowski R, Rabczynski J, Lage H, Surowiak P (2013) MRP2 (ABCC2, cMOAT) expression in nuclear envelope of primary fallopian tube cancer cells is a new unfavorable prognostic factor. Arch Gynecol Obstet 287:563–570CrossRefPubMedPubMedCentralGoogle Scholar
  132. Hara Y, Sassi Y, Guibert C, Gambaryan N, Dorfmüller P, Eddahibi S et al (2011) Inhibition of MRP4 prevents and reverses pulmonary hypertension in mice. J Clin Invest 121:2888–2897CrossRefPubMedPubMedCentralGoogle Scholar
  133. Harrington AM, Castro J, Young RL, Kurtz CB, Silos-Santiago I, Nguyen NQ et al (2014) Distinct alterations in the guanylate cyclase-C (GC-C)/cyclic GMP (cGMP) pathway are evident across different subtypes of irritable bowel syndrome (IBS) patients. Gastroenterology 146:S-537CrossRefGoogle Scholar
  134. Hasegawa Y, Kishimoto S, Takahashi H, Inotsume N, Takeuchi Y, Fukushima S (2009) Altered expression of MRP2, MRP3 and UGT2B1 in the liver affects the disposition of morphine and its glucuronide conjugate in a rat model of cholestasis. J Pharm Pharmacol 61:1205–1210CrossRefPubMedPubMedCentralGoogle Scholar
  135. Hattori H, Suminoe A, Wada M, Koga Y, Kohno K, Okamura J et al (2007) Regulatory polymorphisms of multidrug resistance 1(MDR1) gene are associated with the development of childhood acute lymphoblastic leukemia. Leuk Res 31:1633–1640CrossRefPubMedPubMedCentralGoogle Scholar
  136. Hawwa AF, McKiernan PJ, Shields M, Millership JS, Collier PS, McElnay JC (2009) Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant. Br J Clin Pharmacol 68:413–421CrossRefPubMedPubMedCentralGoogle Scholar
  137. Hazard SE, Patel SB (2007) Sterolins ABCG5 and ABCG8: regulators of whole body dietary sterols. Pflugers Arch 453:745–752CrossRefPubMedPubMedCentralGoogle Scholar
  138. Hedman A, Angelin B, Arvidsson A, Dahlqvist R, Nilsson B (1990) Interactions in the renal and biliary elimination of digoxin: stereoselective difference between quinine and quinidine. Clin Pharmacol Ther 47:20–26CrossRefPubMedPubMedCentralGoogle Scholar
  139. Henderson MJ, Haber M, Porro A, Munoz MA, Iraci N, Xue C et al (2011) ABCC multidrug transporters in childhood neuroblastoma: clinical and biological effects independent of cytotoxic drug efflux. J Natl Cancer Inst 103:1236–1251CrossRefPubMedPubMedCentralGoogle Scholar
  140. Henmi K, Yoshida M, Yoshikawa N, Hirano T (2008) P-glycoprotein functions in peripheral-blood CD4+ cells of patients with systemic lupus erythematosus. Biol Pharm Bull 31:873–878CrossRefPubMedPubMedCentralGoogle Scholar
  141. Higgins CF, Linton KJ (2004) The ATP switch model for ABC transporters. Nat Struct Mol Bio 11:918–926CrossRefGoogle Scholar
  142. Hinz A, Tampé R (2012) ABC Transporters and immunity: mechanism of self-defense. Biochemistry 51:4981–4989CrossRefPubMedPubMedCentralGoogle Scholar
  143. Hirohashi T, Suzuki H, Takikawa H, Sugiyama Y (2000) ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3(Mrp3). J Biol Chem 275:2905–2910CrossRefGoogle Scholar
  144. Hitzl M, Drescher S, van der Kuip H, Schäffeler E, Fischer J, Schwab M et al (2001) The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells. Pharmacogenetics 11:293–298CrossRefPubMedPubMedCentralGoogle Scholar
  145. Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmöller J, Johne A et al (2000) Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A 97:3473–3478CrossRefPubMedPubMedCentralGoogle Scholar
  146. Honjo Y, Hrycyna CA, Yan QW, WY M-P’r, Robey RW, van de Laar A et al (2001) Acquired Mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res 61:6635–6639PubMedPubMedCentralGoogle Scholar
  147. Hopper-Borge EA, Churchill T, Paulose C, Nicolas E, Jacobs JD, Ngo O et al (2011) Contribution of Abcc10 (Mrp7) to in vivo paclitaxel resistance as assessed in Abcc10(−/−) mice. Cancer Res 71:3649–3657CrossRefPubMedPubMedCentralGoogle Scholar
  148. Hosomi A, Nakanishi T, Fujita T, Tamai I (2012) Extra-renal elimination of uric acid via intestinal efflux transporter BCRP/ABCG2. PLoS One 7:e30456CrossRefPubMedPubMedCentralGoogle Scholar
  149. Hu LL, Wang XX, Chen X, Chang J, Li C, Zhang Y et al (2007) BCRP gene polymorphisms are associated with susceptibility and survival of diffuse large B-cell lymphoma. Carcinogenesis 28:1740–1744CrossRefPubMedPubMedCentralGoogle Scholar
  150. Huls M, Russel FGM, Masereeuw R (2009) The role of ATP binding cassette transporters in tissue defense and organ regeneration. J Pharmacol Exp Ther 328:3–9CrossRefPubMedPubMedCentralGoogle Scholar
  151. Huisman MT, Smit JW, Wiltshire HR, Hoetelmans RM, Beijnen JH, Schinkel AH (2001) P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir. Mol Pharmacol 59:806–813CrossRefGoogle Scholar
  152. Huisman MT, Smit JW, Wiltshire HR, Beijnen JH, Schinkel AH (2003) Assessing safety and efficacy of directed P-glycoprotein inhibition to improve the pharmacokinetic properties of saquinavir coadministered with ritonavir. J Pharmacol Exp Ther 304:596–602CrossRefPubMedPubMedCentralGoogle Scholar
  153. Huynh T, Norris MD, Haber M, Henderson MJ (2012) ABCC4/MRP4: MYCN-regulated transporter and potential therapeutic target in neuroblastoma. Front Oncol 2:178CrossRefPubMedPubMedCentralGoogle Scholar
  154. Ichida K, Matsuo H, Takada T, Nakayama A, Murakami K, Shimizu T et al (2012) Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nat Commun 3:764CrossRefPubMedPubMedCentralGoogle Scholar
  155. Imaoka T, Kusuhara H, Adachi M, Schuetz JD, Takeuchi K, Sugiyama Y (2007) Functional involvement of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the renal elimination of the antiviral drugs adefovir and tenofovir. Mol Pharmacol 71:619–627CrossRefPubMedPubMedCentralGoogle Scholar
  156. Ishizuka H, Konno K, Shiina T, Naganuma H, Nishimura K, Ito K, Suzuki H, Sugiyama Y (1999) Species differences in the transport activity for organic anions across the bile canalicular membrane. J Pharmacol Exp Ther 290:1324–1330PubMedPubMedCentralGoogle Scholar
  157. Ito S, Ieiri I, Tanabe M, Suzuki A, Higuchi S, Otsubo K (2001a) Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects. Pharmacogenetics 11:175–184CrossRefPubMedPubMedCentralGoogle Scholar
  158. Ito K, Olsen SL, Qiu W, Deeley RG, Cole SP (2001b) Mutation of a single conserved tryptophan in multidrug resistance protein 1 (MRP1/ABCC1) results in loss of drug resistance and selective loss of organic anion transport. J Biol Chem 276:15616–15624CrossRefGoogle Scholar
  159. Ito S, Iwaki S, Koike K, Yuda Y, Nagasaki A, Ohkawa R et al (2013) Increased plasma sphingosine-1-phosphate in obese individuals and its capacity to increase the expression of plasminogen activator inhibitor-1 in adipocytes. Coron Artery Dis 24:642–650PubMedPubMedCentralGoogle Scholar
  160. Jamroziak K, Młynarski W, Balcerczak E, Mistygacz M, Trelinska J, Mirowski M et al (2004) Functional C3435T polymorphism of MDR1 gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic leukemia. Eur J Haematol 72:314–321CrossRefPubMedPubMedCentralGoogle Scholar
  161. Jansen RS, Mahakena S, de Haas M, Borst P, van de Wetering K (2015) ATP-binding cassette subfamily C member 5 (ABCC5) functions as an efflux transporter of glutamate conjugates and analogs. J Biol Chem 290:30429–30440CrossRefPubMedPubMedCentralGoogle Scholar
  162. Jedlitschky G, Burchell B, Keppler D (2000) The Multidrug resistance protein 5 functions as an atp-dependent export pump for cyclic nucleotides. J Biol Chem 275:30069–30074CrossRefPubMedPubMedCentralGoogle Scholar
  163. Jedlitschky G, Cattaneo M, Lubenow LE, Rosskopf D, Lecchi A, Artoni A et al (2010) Role of MRP4 (ABCC4) in platelet adenine nucleotide-storage: evidence from patients with delta-storage pool deficiencies. Am J Pathol 176:1097–1103CrossRefPubMedPubMedCentralGoogle Scholar
  164. Jedlitschky G, Tirschmann K, Lubenow LE, Nieuwenhuis HK, Akkerman JW, Greinacher A et al (2004) The nucleotide transporter MRP4 (ABCC4) is highly expressed in human platelets and present in dense granules, indicating a role in mediator storage. Blood 104:3603–3610CrossRefPubMedPubMedCentralGoogle Scholar
  165. Jin F, Zhao L, Zhao HY, Guo SG, Feng J, Jiang XB et al (2008) Comparison between cells and cancer stem-like cells isolated from glioblastoma and astrocytoma on expression of anti-apoptotic and multidrug resistance-associated protein genes. Neuroscience 154:541–550CrossRefPubMedPubMedCentralGoogle Scholar
  166. Jing X, Liu X, Wen T, Xie S, Yao D, Liu X et al (2010) Combined effect of epileptic seizure and drug induction resulted in overexpression of P-glycoprotein in brain of kindled rats. Brit J Pharmacol 159:1511–1522CrossRefGoogle Scholar
  167. Johne A, Köpke K, Gerloff T, Mai I, Rietbrock S, Meisel C et al (2002) Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene. Clin Pharmacol Ther 72:584–594CrossRefPubMedPubMedCentralGoogle Scholar
  168. Johnson DR, Finch RA, Lin ZP, Zeiss CJ, Sartorelli AC (2001) The pharmacological phenotype of combined multidrug-resistance mdr1a/1b- and mrp1-deficient mice. Cancer Res 61:1469–1476PubMedPubMedCentralGoogle Scholar
  169. Jones DC, Duvauchelle C, Ikegami A, Olsen CM, Lau SS, de la Torre R et al (2005) Serotonergic neurotoxic metabolites of ecstasy identified in rat brain. J Pharmacol Exp Ther 313:422–431CrossRefPubMedPubMedCentralGoogle Scholar
  170. Jonker JW, Buitelaar M, Wagenaar E, Van Der Valk MA, Scheffer GL, Scheper RJ et al (2002) The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci U S A 99:15649–15654CrossRefPubMedPubMedCentralGoogle Scholar
  171. Jonker JW, Smit JW, Brinkhuis RF, Maliepaard M, Beijnen JH et al (2000) Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst 92:1651–1656CrossRefGoogle Scholar
  172. Kamisako T, Ogawa H (2005) Alteration of the expression of adenosine triphosphate-binding cassette transporters associated with bile acid and cholesterol transport in the rat liver and intestine during cholestasis. J Gastroenterol Hepatol 20:1429–1434CrossRefPubMedPubMedCentralGoogle Scholar
  173. Kathawala RJ, Sodani K, Chen K, Patel A, Abuznait AH, Anreddy N, Sun YL et al (2014) Masitinib antagonizes ATP-binding cassette subfamily C member 10-mediated paclitaxel resistance: a preclinical study. Mol Cancer Ther 13:714–723CrossRefPubMedPubMedCentralGoogle Scholar
  174. Kathawala RJ, Wei L, Anreddy N, Anreddy N, Chen K, Patel A et al (2015) The small molecule tyrosine kinase inhibitor NVP-BHG712 antagonizes ABCC10-mediated paclitaxel resistance: a preclinical and pharmacokinetic study. Oncotarget 6:510–521CrossRefGoogle Scholar
  175. Kawaguchi K, Okamoto T, Morita M, Imanaka T (2016) Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1. Sci Rep 6:30183CrossRefPubMedPubMedCentralGoogle Scholar
  176. Kemp S, Berger J, Aubourg P (2012) X-linked adrenoleukodystrophy: Clinical, metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta 1822:1465–1474CrossRefGoogle Scholar
  177. Kim YH, Ishii G, Goto K, Ota S, Kubota K, al MY (2009a) Expression of breast cancer resistance protein is associated with a poor clinical outcome in patients with small-cell lung cancer. Lung Cancer 65:105–111CrossRefGoogle Scholar
  178. Kim DH, Sriharsha L, Xu W, Kamel-Reid S, Liu X, Siminovitch K et al (2009b) Clinical relevance of a pharmacogenetic approach using multiple candidate genes to predict response and resistance to imatinib therapy in chronic myeloid leukemia. Clin Cancer Res 15:4750–4758CrossRefGoogle Scholar
  179. Kim JC, Lee NC, Hwu PW, Chien YH, Fahiminiya S, Majewski J et al (2012) Late onset of symptoms in an atypical patient with the cblJ inborn error of vitamin B12 metabolism: diagnosis and novel mutation revealed by exome sequencing. Mol Genet Metab 107:664–668CrossRefPubMedPubMedCentralGoogle Scholar
  180. Kitamura Y, Hirouchi M, Kusuhara H, Schuetz JD, Sugiyama Y (2008) Increasing systemic exposure of methotrexate by active efflux mediated by multidrug resistance-associated protein 3 (Mrp3/Abcc3). J Pharmacol Exp Ther 327:465–473CrossRefPubMedPubMedCentralGoogle Scholar
  181. Kitamura Y, Kusuhara H, Sugiyama Y (2010) Basolateral efflux mediated by multidrug resistance-associated protein 3(Mrp3/Abcc3) facilitates intestinal absorption of folates in mouse. Pharm Res 27:665–672CrossRefPubMedPubMedCentralGoogle Scholar
  182. Kobuchi H, Moriya K, Ogino T, Fujita H, Inoue K, Shuin T et al (2012) Mitochondrial localization of ABC transporter ABCG2 and Its function in 5-aminolevulinic acid-mediated protoporphyrin IX accumulation. PLoS One 7:e50082CrossRefPubMedPubMedCentralGoogle Scholar
  183. Kochel TJ, Olga G, Goloubeva QG, Fulton AM (2016) Upregulation of cyclooxygenase-2 /prostaglandin E2 (COX-2/PGE2) pathway member multiple drug resistance-associated protein 4 (MRP4) and downregulation of prostaglandin transporter (PGT) and 15-prostaglandin dehydrogenase (15-PGDH) in triple-negative breast cancer. Breast Cancer (Auckl) 10:61–70Google Scholar
  184. Kochel TJ, Fulton AM (2015) Multiple drug resistance-associated protein 4 (MRP4), prostaglandin transporter (PGT), and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) as determinants of PGE2 levels in cancer. Prostaglandins Other Lipid Mediat 116–117:99–103CrossRefPubMedPubMedCentralGoogle Scholar
  185. Kohler JJ, Hosseini SH, Green E, Abuin A, Ludaway T, Russ R et al (2011) Tenofovir renal proximal tubular toxicity is regulated by OAT1 and MRP4 transporters. Lab Investig 91:852–858CrossRefGoogle Scholar
  186. Komoto C, Nakamura T, Sakaeda T, Kroetz DL, Yamada T, Omatsu H et al (2006) MDR1 haplotype frequencies in Japanese and Caucasian, and in Japanese patients with colorectal cancer and esophageal cancer. Drug Metab Pharmacokinet 21:126–132CrossRefGoogle Scholar
  187. Konig J, Rost D, Cui Y, Keppler D (1999) Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane. Hepatology 29:1156–1163CrossRefGoogle Scholar
  188. Koo DH, Ryu MH, Ryoo BY, Beck MY, Na YS, Shin JG et al (2015) Association of ABCG2 polymorphism with clinical efficacy of imatinib in patients with gastrointestinal stromal tumor. Cancer Chemother Pharmacol 75:173–182CrossRefGoogle Scholar
  189. Kooij G, Backer R, Koning JJ, Reijerkerk A, van Horssen J, van der Pol SM et al (2009) P-glycoprotein acts as an immunomodulator during neuroinflammation. PLoS One 4:e8212CrossRefPubMedPubMedCentralGoogle Scholar
  190. Kooij G, van Horssen J, de Lange EC, Reijerkerk A, van der Pol SM, van Het Hof B et al (2010) T lymphocytes impair P-glycoprotein function during neuroinflammation. J Autoimmun 34:416–425CrossRefGoogle Scholar
  191. Kool M, de Haas M, Scheffer GL, Scheper RJ, van Eijk MJ, Juijn JA et al (1997) Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res 57:3537–3547PubMedGoogle Scholar
  192. Korenaga Y, Naito K, Okayama N, Hirata H, Suehiro Y, Hamanaka Y et al (2005) Association of the BCRP C421A polymorphism with nonpapillary renal cell carcinoma. Int J Cancer 117:431–434CrossRefGoogle Scholar
  193. Korita PV, Wakai T, Shirai Y, Matsuda Y, Sakata J, Takamura M et al (2010) Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma. Oncol Rep 23:965–972PubMedGoogle Scholar
  194. Koziolek MJ, Riess R, Geiger H, Thévenod F, Hauser IA (2001) Expression of multidrug resistance P-glycoprotein in kidney allografts from cyclosporine A-treated patients. Kidney Int 60:156–166CrossRefGoogle Scholar
  195. Krishnamurthy P, Ross DD, Nakanishi T, Bailey-Dell K, Zhou S, Mercer KE et al (2004) The Stem Cell Marker Bcrp/ABCG2 Enhances Hypoxic Cell Survival through Interactions with Heme. J Bio Chem 279:24218–24225CrossRefGoogle Scholar
  196. Krishnamurthy P, Schuetz JD (2011) The role of ABCG2 and ABCB6 in porphyrin metabolism and cell survival. Curr Pharm Biotechnol 12:647–655CrossRefPubMedPubMedCentralGoogle Scholar
  197. Krishnamurthy P, Schwab M, Takenaka K, Nachagari D, Morgan J, Leslie M et al (2008) Transporter-mediated protection against thiopurine-induced hematopoietic toxicity. Cancer Res 68:4983–4989CrossRefPubMedPubMedCentralGoogle Scholar
  198. Kubitz R, Dröge C, Stindt J, Weissenberger K, Häussinger D (2012) The bile salt export pump (BSEP) in health and disease. Clin Res Hepatol Gastroenterol 36:536–553CrossRefPubMedPubMedCentralGoogle Scholar
  199. Kusuhara H, Sugiyama Y (2007) ATP-binding cassette, subfamily G (ABCG family). Pflugers Arch 453:735–744CrossRefPubMedPubMedCentralGoogle Scholar
  200. Kuan CT, Wakiya K, Herndon JE II, Lipp ES, Pegram CN, Riggins GJ et al (2010) MRP3: a molecular target for human glioblastoma multiforme immunotherapy. BMC Cancer 10:468CrossRefPubMedPubMedCentralGoogle Scholar
  201. Kurzawski M, Bartnicka L, Florczak M, Górnik W, Droździk M (2007) Impact of ABCB1 (MDR1) gene polymorphism and P-glycoprotein inhibitors on digoxin serum concentration in congestive heart failure patients. Pharmacol Rep 59:107–111PubMedPubMedCentralGoogle Scholar
  202. Lang T, Justenhoven C, Winter S, Baisch C, Hamann U, Harth V et al (2011) The earwax- associated SNP c.538G>A (G180R) in ABCC11 is not associated with breast cancer risk in Europeans. Breast Cancer Res Treat 129:993–999CrossRefPubMedPubMedCentralGoogle Scholar
  203. Lee J, Wang R, Yang Y, Lu X, Zhang X, Wang L, Lou Y (2015) The effect of ABCB1 C3435T polymorphism on cyclosporine dose requirements in kidney transplant recipients: a meta-analysis. Basic Clin Pharmacol Toxicol 117:117–125CrossRefPubMedPubMedCentralGoogle Scholar
  204. Lee JS, Jung ID, Lee CM, Noh KT, Park JW, Son KH et al (2011) Venlafaxine inhibits the development and differentiation of dendritic cells through the regulation of P-glycoprotein. Int Immunopharmacol 11:1348–1357CrossRefPubMedPubMedCentralGoogle Scholar
  205. Lemos C, Giovannetti E, Zucali PA, Assaraf YG, Scheffer GL, van der Straaten T (2011) Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients. Pharmacogenomics 12:159–170CrossRefPubMedPubMedCentralGoogle Scholar
  206. Leslie EM (2012) Arsenic-glutathione conjugate transport by the human multidrug resistance proteins (MRPs/ABCCs). J Inorg Biochem 108:141–149CrossRefPubMedPubMedCentralGoogle Scholar
  207. Leslie EM, Deeley RG, Cole SPC (2005) Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 204:216–237CrossRefPubMedPubMedCentralGoogle Scholar
  208. Li H, Karl T, Garner B (2015) Understanding the function of ABCA7 in Alzheimer’s disease. Biochem Soc Trans 43:920–923CrossRefPubMedPubMedCentralGoogle Scholar
  209. Li C, Krishnamurthy PC, Penmatsa H, Marrs KL, Wang XQ, Zaccolo M et al (2007) Spatiotemporal coupling of cAMP transporter to CFTR chloride channel function in the gut epithelia. Cell 131:940–951CrossRefPubMedPubMedCentralGoogle Scholar
  210. Li J, Li ZN, Yu LC, Bao QL, Wu JR, Shi SB et al (2010) Association of expression of MRP1, BCRP, LRP and ERCC1 with outcome of patients with locally advanced non-small cell lung cancer who received neoadjuvant chemotherapy. Lung Cancer 69:116–122CrossRefPubMedPubMedCentralGoogle Scholar
  211. Li N, Zhang Y, Hua F, Lai Y (2009) Absolute difference of hepatobiliary transporter multidrug resistance-associated protein (MRP2/Mrp2) in liver tissues and isolated hepatocytes from rat, dog, monkey, and human. Drug Metab Dispos 37:66–73CrossRefPubMedPubMedCentralGoogle Scholar
  212. Liang SC, Yang CY, Tseng JY, Wang HL, Tung CY, Liu HW et al (2015) ABCG2 localizes to the nucleus and modulates cdh1 expression in lung cancer cells. Neoplasia 17:265–278CrossRefPubMedPubMedCentralGoogle Scholar
  213. Lickteig AJ, Fisher CD, Augustine LM, Aleksunes LM, Besselsen DG, Slitt AL, Manautou JE et al (2007) Efflux transporter expression and acetaminophen metabolite excretion are altered in rodent models of nonalcoholic fatty liver disease. Drug Metab Dispos 35:1970–1978CrossRefPubMedPubMedCentralGoogle Scholar
  214. Lin JH, Yamazaki M (2003) Clinical relevance of P-glycoprotein in drug therapy. Drug Metab Rev 35:417–454CrossRefGoogle Scholar
  215. Lindberg-Freijs A, Karlsson MO (1994) Dose dependent absorption and linear disposition of cyclosporine A in rat. Biopharm Drug Dispos 15:75–86CrossRefPubMedPubMedCentralGoogle Scholar
  216. Liu H, Zhang D, Xu X, Liu X, Wang G, Xie L et al (2007) Attenuated function and expression of P-glycoprotein at blood-brain barrier and increased brain distribution of phenobarbital in streptozotocin-induced diabetic mice. Euro J Pharmacol 561:226–232CrossRefGoogle Scholar
  217. Liu L, Liu XD (2014) Alterations in function and expression of ABC transporters at blood-brain barrier under diabetes and the clinical significances. Front Pharmacol 5:273CrossRefPubMedPubMedCentralGoogle Scholar
  218. Liu XD, Zhang L, Xie L (2003) Effect of P-glycoprotein inhibitors erythromycin and cyclosporine A on brain pharmacokinetics of nimodipine in rats. Eur J Drug Metab Pharmacokinet 28:309–313CrossRefPubMedPubMedCentralGoogle Scholar
  219. Liu XD, Pan GY, Xie L, Hou YY, Lan W, Su Q et al (2002) Cyclosporin A enhanced protection of nimodipine against brain damage induced by hypoxia-ischemia in mice and rats. Acta Pharmacol Sin 23:225–229PubMedPubMedCentralGoogle Scholar
  220. Liu Y, Yin Y, Sheng Q, Lu X, Wang F, Lin Z et al (2014) Association of ABCC2 224C.T polymorphism with High-dose methotrexate plasma concentrations and toxicities in childhood acute lymphoblastic leukemia. PLoS One 9:e82681CrossRefPubMedPubMedCentralGoogle Scholar
  221. Llaudó I, Colom H, Giménez-Bonafé P, Torras J, Caldés A, Sarrias M et al (2013) Do drug transporter (ABCB1) SNPs and P-glycoprotein function influence cyclosporine and macrolides exposure in renal transplant patients? Results of the pharmacogenomics substudy within the symphony study. Transpl Int 26:177–186CrossRefPubMedPubMedCentralGoogle Scholar
  222. Loging WT, Lal A, Siu IM, Loney TL, Carol J, Wikstrand CJ et al (2000) Identifying potential tumor markers and antigens by database mining and rapid expression screening. Genome Res 10:1393–1402CrossRefPubMedPubMedCentralGoogle Scholar
  223. Loh PT, Lou HX, Zhao Y, Chin YM, Vathsala A (2008) Significant impact of gene polymorphisms on tacrolimus but not cyclosporine dosing in Asian renal transplant recipients. Transplant Proc 40:1690–1695CrossRefPubMedPubMedCentralGoogle Scholar
  224. Low SK, Fukunaga K, Takahashi A, Matsuda K, Hongo F et al (2016) Association study of a functional variant on ABCG2 gene with sunitinib-induced severe adverse drug reaction. PLoS One 11:e0148177CrossRefPubMedPubMedCentralGoogle Scholar
  225. Lynch J, Fukuda Y, Krishnamurthy P, Du G, Schuetz JD (2009) Cell survival under stress is enhanced by a mitochondrial ATP-binding cassette transporter that regulates hemoproteins. Cancer Res 69:5560–5567CrossRefPubMedPubMedCentralGoogle Scholar
  226. Maciejczyk A, Jagoda E, Wysocka T, Matkowski R, Györffy B, Lage H et al (2012) ABCC2 (MRP2, cMOAT) localized in the nuclear envelope of breast carcinoma cells correlates with poor clinical outcome. Pathol Oncol Res 18:331–342CrossRefPubMedPubMedCentralGoogle Scholar
  227. Maeno K, Nakajima A, Conseil G, Rothnie A, Deeley RG, Cole SPC (2009) Molecular basis for reduced estrone sulfate transport and altered modulator sensitivity of transmembrane helix (TM) 6 and TM17 mutants of multidrug resistance protein 1 (ABCC1). Drug Metabo Dispo 37:1411–1420CrossRefGoogle Scholar
  228. Malingré MM, Beijnen JH, Rosing H, Koopman FJ, Jewell RC, Paul EM et al (2001) Co-administration of GF120918 significantly increases the systemic exposure to oral paclitaxel in cancer patients. Br J Cancer 84:42–47CrossRefPubMedPubMedCentralGoogle Scholar
  229. Mao Q, Unadkat JD (2014) Role of the breast cancer resistance protein (BCRP/ABCG2) in drug transport—an update. AAPS J 17:65–82CrossRefPubMedPubMedCentralGoogle Scholar
  230. Marzolini C, Rudin C, Decosterd LA, Telenti A, Schreyer A, Biollaz J et al (2002) Transplacental passage of protease inhibitors at delivery. AIDS 16:889–893CrossRefPubMedPubMedCentralGoogle Scholar
  231. Massimi I, Ciuffetta A, Temperilli F, Ferrandino F, Zicari A, Pulcinelli FM et al (2015) Multidrug resistance protein-4 influences aspirin toxicity in human cell line. Mediat Inflamm 2015:607957CrossRefGoogle Scholar
  232. Massimi I, Guerriero R, Lotti LV, Lulli V, Borgognone A, Romani F et al (2014) Aspirin influences megakaryocytic gene expression leading to up-regulation of multidrug resistance protein-4 in human platelets. Br J Clin Pharmacol 78:1343–1353CrossRefPubMedPubMedCentralGoogle Scholar
  233. Masunaga Y, Noto T, Suzuki K, Takahashi K, Shimizu Y, Morokata T (2007) Expression profiles of cytokines and chemokines in murine Mdr1a−/− colitis. Inflamm Res 56:439–446CrossRefPubMedPubMedCentralGoogle Scholar
  234. Matsuo H, Takada T, Ichida K, Nakamura T, Nakayama A, Suzuki H et al (2011) ABCG2/BCRP dysfunction as a major cause of gout. Nucleosides Nucleotides Nucleic Acids 30:1117–11128CrossRefPubMedPubMedCentralGoogle Scholar
  235. Matsuo H, Tsunoda T, Ooyama K, Sakiyama M, Sogo T, Takada T et al (2016) Hyperuricemia in acute gastroenteritis is caused by decreased urate excretion via ABCG2. Sci Rep 6:31003CrossRefPubMedPubMedCentralGoogle Scholar
  236. Mattiello T, Guerriero R, Lotti LV, Trifirò E, Felli MP, Barbarulo A et al (2011) Aspirin extrusion from human platelets through multidrug resistance protein-4-mediated transport: evidence of a reduced drug action in patients after coronary artery bypass grafting. J Am Coll Cardiol 58:752–761CrossRefPubMedPubMedCentralGoogle Scholar
  237. Mayer U, Wagenaar E, Beijnen JH, Smit JW, Meijer DK, van Asperen J et al (1996) Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr 1a P-glycoprotein. Br J Pharmacol 119:1038–1044CrossRefPubMedPubMedCentralGoogle Scholar
  238. McGill MR, Jaeschke H (2013) Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res 30:2174–2187CrossRefPubMedPubMedCentralGoogle Scholar
  239. Meijer OC, de Lange EC, Breimer DD, de Boer AG, Workel JO, de Kloet ER (1998) Penetration of dexamethasone into brain glucocorticoid targets is enhanced in mdr1A P-glycoprotein knockout mice. Endocrinology 139:1789–1793CrossRefPubMedPubMedCentralGoogle Scholar
  240. Melguizo C, Prados J, Luque R, Ortiz R, Caba O, Álvarez PJ et al (2012) Modulation of MDR1 and MRP3 gene expression in lung cancer cells after paclitaxel and carboplatin exposure. Int J Mol Sci 13:16624–16635CrossRefPubMedPubMedCentralGoogle Scholar
  241. Mendes J, Martinho A, Simoes O, Mota A, Breitenfeld L, Pais L (2009) Genetic polymorphism in CYP3A5 and MDR1 genes and their correlation with plasma levels of tacrolimus and cyclosporine in renal transplant recipients. Transplant Proc 41:840–842CrossRefPubMedPubMedCentralGoogle Scholar
  242. Merino G, Alvarez AI, Pulido MM, Molina AJ, Schinkel AH, Prieto JG (2006) Breast cancer resistance protein (BCRP/ABCG2) transports fluoroquinolone antibiotics and affects theiroral availability, pharmacokinetics, and milk secretion. Drug Metab Dispos 34:690–695CrossRefPubMedPubMedCentralGoogle Scholar
  243. Merino G, Jonker JW, Wagenaar E, van Herwaarden AE, Schinkel AH (2005) The breast cancer resistance protein (BCRP/ABCG2) affects pharmacokinetics, hepatobiliary excretion, and milk secretion of the antibiotic nitrofurantoin. Mol Pharmacol 67:1758–1764CrossRefPubMedPubMedCentralGoogle Scholar
  244. Meyer Z, Schwabedissen HE, Grube M, Heydrich B, Linnemann K, Fusch C, Kroemer HK et al (2005) Expression, localization, and function of MRP5(ABCC5), a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts: effects of gestational age and cellular differentiation. Am J Pathol 166:39–48CrossRefGoogle Scholar
  245. Mistry P, Stewart AJ, Dangerfield W, Okiji S, Liddle C, Bootle D et al (2001) In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576. Cancer Res 61:749–758PubMedPubMedCentralGoogle Scholar
  246. Mitra P, Oskeritzian CA, Payne SG, Beaven MA, Milstien S, Spiegel S (2006) Role of ABC1 in export of sphingosine-1-phosphate from mast cells. Proc Natl Acad Sci U S A 103:16394–16399CrossRefPubMedPubMedCentralGoogle Scholar
  247. Molday RS, Zhong M, Quazi F (2009) The Role of the photoreceptor ABC transporter ABCA4 in lipid transport and Stargardt Macular degeneration. Biochim Biophys Acta 1791:573–583CrossRefPubMedPubMedCentralGoogle Scholar
  248. Moon C, Zhang W, Ren A, Arora K, Sinha C, Yarlagadda S et al (2015) Compartmentalized accumulation of cAMP near complexes of multidrug resistance protein 4 (MRP4) and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) contributes to drug-induced diarrhea. J Biol Chem 290:11246–11257CrossRefPubMedPubMedCentralGoogle Scholar
  249. Morisaki K, Robey RW, Ozvegy-Laczka C, Honjo Y, Polgar O, Steadman K et al (2005) Single nucleotide polymorphisms modify the transporter activity of ABCG2. Cancer Chemother Pharmacol 56:161–172CrossRefGoogle Scholar
  250. Mouly S, Paine MF (2003) P-glycoprotein increases from proximal to distal regions of human small intestine. Pharm Res 20:1595–1599CrossRefPubMedPubMedCentralGoogle Scholar
  251. Myint K, Li Y, James Paxton J, Mark McKeage M (2015) Multidrug resistance-associated protein 2 (MRP2) mediated transport of oxaliplatin-derived platinum in membrane vesicles. PLoS One 10:e0130727CrossRefPubMedPubMedCentralGoogle Scholar
  252. 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 49:482–489CrossRefPubMedPubMedCentralGoogle Scholar
  253. Nakayama A, Matsuo H, Takada T, Ichida K, Nakamura T, Ikebuchi Y et al (2011) ABCG2 is a high-capacity urate transporter and its genetic impairment increases serum uric acid levels in humans. Nucleosides Nucleotides Nucleic Acids 30:1091–1097CrossRefPubMedPubMedCentralGoogle Scholar
  254. Nakayama A, Matsuo H, Nakaoka H, Nakamura T, Nakashima H, Takada Y et al (2014) Common dysfunctional variants of ABCG2 have stronger impact on hyperuricemia progression than typical environmental risk factors. Sci Rep 4:5227CrossRefPubMedPubMedCentralGoogle Scholar
  255. Newman MJ, Rodarte JC, Benbatoul KD, Romano SJ, Zhang C, Krane S et al (2000) Discovery and characterization of OC144-093, a novel inhibitor of P-glycoprotein-mediated multidrug resistance. Cancer Res 60:2964–2972PubMedPubMedCentralGoogle Scholar
  256. Niemeijer MN, van den Berg ME, Deckers JW, Aarnoudse AL, Hofman A, Franco OH et al (2015) ABCB1 gene variants, digoxin and risk of sudden cardiac death in a general population. Heart 101:1973–1979CrossRefPubMedPubMedCentralGoogle Scholar
  257. Nicolaou M, Andress EJ, Zolnerciks JK, Dixon PH, Williamson C, Linton KJ (2012) Canalicular ABC transporters and liver disease. J Pathol 226:300–315CrossRefPubMedPubMedCentralGoogle Scholar
  258. Nies AT, Keppler D (2007) The apical conjugate efflux pump ABCC2 (MRP2). Pflügers Arch 453:643–659CrossRefPubMedPubMedCentralGoogle Scholar
  259. Nones K, Dommels YE, Martell S, Butts C, McNabb WC, Park ZA et al (2009a) The effects of dietary curcumin and rutin on colonic inflammation and gene expression in multidrug resistance gene-deficient (Mdr1a−/−) mice, a model of inflammatory bowel diseases. Br J Nutr 101:169–181CrossRefPubMedPubMedCentralGoogle Scholar
  260. Nones K, Knoch B, Dommels YE, Paturi G, Butts C, McNabb WC et al (2009b) Multidrug resistance gene deficient (Mdr1a−/−) mice have an altered caecal microbiota that precedes the onset of intestinal inflammation. J Appl Microbiol 107:557–566CrossRefPubMedPubMedCentralGoogle Scholar
  261. Nunoya K, Grant CE, Zhang D, Cole SP, Deeley RG (2003) Molecular cloning and pharmacological characterization of rat multidrug resistance protein 1 (mrp1). Drug Metab Dispos 31:1016–1026CrossRefPubMedPubMedCentralGoogle Scholar
  262. Ogawa K, Suzuki H, Hirohashi T, Ishikawa T, Meier PJ, Hirose K et al (2000) Characterization of inducible nature of Mrp3 in rat liver. Am J Physiol Gastrointest Liver Physiol 278:G438–G446CrossRefPubMedPubMedCentralGoogle Scholar
  263. Oh GS, Kim HJ, Shen A, Lee SB, Yang SH, Shim H et al (2016) New therapeutic concept of NAD redox balance for cisplatin nephrotoxicity. Biomed Res Int 2016:4048390PubMedPubMedCentralGoogle Scholar
  264. Oevermann L, Scheitz J, Starke K, Köck K, Kiefer T, Dölken G et al (2009) Hematopoietic stem cell differentiation affects expression and function of MRP4(ABCC4), a transport protein for signaling molecules and drugs. Int J Cancer 124:2303–2311CrossRefPubMedPubMedCentralGoogle Scholar
  265. Okamura N, Hirai M, Tanigawara Y, Tanaka K, Yasuhara M, Ueda K et al (1993) Digoxin-cyclosporin A interaction: modulation of the multidrug transporter P-glycoprotein in the kidney. J Pharmacol Exp Ther 266:1614–1619PubMedPubMedCentralGoogle Scholar
  266. Oguri T, Bessho Y, Achiwa H, Ozasa H, Maeno K, Maeda H et al (2007) MRP8/ABCC11 directly confers resistance to 5-fluorouracil. Mol Cancer Ther 6:122–127CrossRefPubMedPubMedCentralGoogle Scholar
  267. Oguri T, Isobe T, Suzuki T, Nishio K, Fujiwara Y, Katoh O et al (2000) Increased expression of the MRP5 gene is associated with exposure to platinum drugs in lung cancer. Int J Cancer 86:95–100CrossRefPubMedPubMedCentralGoogle Scholar
  268. Ota I, Sakurai A, Toyoda Y, Morita S, Sasaki T, Chishima T et al (2010) Association between breast cancer risk and the wild-type allele of human ABC transporter ABCC11. Anticancer Res 30:5189–5194PubMedPubMedCentralGoogle Scholar
  269. Ota S, Ishii G, Goto K, Kubota K, Kim YH, Kojika M et al (2009) Immunohistochemical expression of BCRP and ERCC1 in biopsy specimen predicts survival in advanced non small cell lung cancer treated with cisplatin-based chemotherapy. Lung Cancer 64:98–104CrossRefPubMedPubMedCentralGoogle Scholar
  270. Quazi F, Molday RS (2014) ATP-binding cassette transporter ABCA4 and chemical isomerization protect photoreceptor cells from the toxic accumulation of excess 11-cis-retinal. Proc Natl Acad Sci U S A 111:5024–5029CrossRefPubMedPubMedCentralGoogle Scholar
  271. Oude Elferink RPJ, Paulusma CC (2007) Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein). Pflugers Arch 453:601–610CrossRefPubMedPubMedCentralGoogle Scholar
  272. Panwala CM, Jones JC, Viney JL (1998) A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J Immunol 161:5733–5744PubMedPubMedCentralGoogle Scholar
  273. Peca D, Cutrera R, Masotti A, Boldrini R, Danhaive O (2015) ABCA3, a key player in neonatal respiratory transition and genetic disorders of the surfactant system. Biochem Soc Trans 43:913–919CrossRefGoogle Scholar
  274. Picchianti-Diamanti A, Rosado MM, Scarsella M, Laganà B, D’Amelio R (2014) P-glycoprotein and drug resistance in systemic autoimmune diseases. Int J Mol Sci 15:4965–4976CrossRefPubMedPubMedCentralGoogle Scholar
  275. Piehler AP, Özcürümez M, Kaminski WE (2012) A-Subclass ATP-Binding Cassette Proteins in Brain Lipid Homeostasis and Neurodegeneration. Front Psych 3:17Google Scholar
  276. Piñeiro R, Maffucci T, Falasca M (2011) The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. Oncogene 30:142–152CrossRefPubMedPubMedCentralGoogle Scholar
  277. Plasschaert SL, de Bont ES, Boezen M, vander Kolk DM, Daenen SM, Faber KN et al (2005) Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia. Clin Cancer Res 11:8661–8668CrossRefPubMedPubMedCentralGoogle Scholar
  278. Porro A, Haber M, Diolaiti D, Iraci N, Henderson M, Gherardi S et al (2010) Direct and coordinate regulation of ATP-binding cassette transporter genes by Myc factors generates specific transcription signatures that significantly affect the chemoresistance phenotype of cancer cells. J Biol Chem 285:19532–19543CrossRefPubMedPubMedCentralGoogle Scholar
  279. Prasad KN, Cole WC, Yan XD, Nahreini P, Kumar B, Hanson A et al (2003) Defects in cAMP-pathway may initiate carcinogenesis in dividing nerve cells: a review. Apoptosis 8:579–586CrossRefPubMedPubMedCentralGoogle Scholar
  280. Puntoni M, Sbrana F, Bigazzi F, Sampietro T (2012) Tangier disease: epidemiology, pathophysiology, and management. Am J Cardiovasc Drugs 12:303–311CrossRefGoogle Scholar
  281. Raggers RJ, Vogels I, van MG (2001) Multidrug-resistance P-glycoprotein (MDR1) secretes platelet-activating factor. Biochem J 357:859–865CrossRefPubMedPubMedCentralGoogle Scholar
  282. Rahgozar S, Moafi A, Abedi M, Entezar-E-Ghaem M, Moshtaghian J, Ghaedi K et al (2014) mRNA expression profile of multidrug-resistant genes in acute lymphoblastic leukemia of children, a prognostic value for ABCA3 and ABCA2. Cancer Biol Ther 15:35–41CrossRefGoogle Scholar
  283. Rasmuson A, Kock A, Fuskevåg OM, Kruspig B, Simón-Santamaría J, Gogvadze V et al (2012) Autocrine prostaglandin E2 signaling promotes tumor cell survival and proliferation in childhood neuroblastoma. PLoS One 7:e29331CrossRefPubMedPubMedCentralGoogle Scholar
  284. Rengelshausen J, Göggelmann C, Burhenne J, Riedel KD, Ludwig J, Weiss J et al (2003) Contribution of increased oral bioavailability and reduced nonglomerular renal clearance of digoxin to the digoxin-clarithromycin interaction. Br J Clin Pharmacol 56:32–38CrossRefPubMedPubMedCentralGoogle Scholar
  285. Rijavec M, Šilar M, Triller N, Kern I, Čegovnik U, Košnik M et al (2011) Expressions of topoisomerase IIα and BCRP in metastatic cells are associated with overall survival in small cell lung cancer patients. Pathol Oncol Res 17:691–696CrossRefPubMedPubMedCentralGoogle Scholar
  286. Robey RW, Honjo Y, Morisaki K, Nadjem TA, Runge S, Risbood M et al (2003) Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity. Bri J Cancer 89:1971–1978CrossRefGoogle Scholar
  287. Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kélaïdi C, Blanche P (2004) Acute colchicine intoxication during clarithromycin administration. Ann Pharmacother 38:2074–2077CrossRefPubMedPubMedCentralGoogle Scholar
  288. Schaeffeler E, Eichelbaum M, Brinkmann U, Penger A, Asante-Poku S, Zanger UM et al (2001) Frequency of C3435T polymorphism of MDR1 gene in African people. Lancet 358:383–384CrossRefPubMedPubMedCentralGoogle Scholar
  289. Sakaeda T, Nakamura T, Horinouchi M, Kakumoto M, Ohmoto N, Sakai T et al (2001) MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects. Pharm Res 18:1400–1404CrossRefPubMedPubMedCentralGoogle Scholar
  290. Salimizand H, Amini S, Abdi M, Ghaderi B, Azadi NA (2016) Concurrent effects of ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp genetic polymorphisms with risk of cancer, clinical output, and response to treatment with imatinib mesylate in patients with chronic myeloid leukemia. Tumor Biol 37:791–798CrossRefGoogle Scholar
  291. Sanchez S, Jimenez C, Carrera AC, Diaz-Nido J, Avila J, Wandosell F (2004) A cAMP-activated pathway, including PKA and PI3K, regulates neuronal differentiation. Neurochem Int 44:231–242CrossRefPubMedPubMedCentralGoogle Scholar
  292. Schaich M, Soucek S, Thiede C, Ehninger G, Illmer T (2005) MDR1 and MRP1 gene expression are independent predictors for treatment outcome in adult acute myeloid leukaemia. Br J Haemato 128:324–332CrossRefGoogle Scholar
  293. Scharenberg CW, Harkey MA, Torok-Storb B (2002) The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood 99:507–512CrossRefPubMedPubMedCentralGoogle Scholar
  294. Schinkel AH, Smit JJ, van Tellingen O, Beijnen JH, Wagenaar E, van Deemter L et al (1994) Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994(77):491–450Google Scholar
  295. Schinkel AH, Jonker JW (2012) Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev 64:138–153CrossRefGoogle Scholar
  296. Schuetz JD, Connelly MC, Sun D, Paibir SG, Flynn PM, Srinivas RV et al (1999) MRP4: a previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nat Med 5:1048–1051CrossRefGoogle Scholar
  297. Schulz T, Schumacher U, Christian Prante C, Sextro W, Prehm P (2010) Cystic fibrosis transmembrane conductance regulator can export hyaluronan. Pathobiology 77:200–209CrossRefGoogle Scholar
  298. Schulz T, Schumacher U, Prehm P (2007) Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular cGMP. J Biol Chem 282:20999–21004CrossRefGoogle Scholar
  299. Scialis RJ, Csanaky IL, IL GMJ, Manautou JE (2015) Multidrug resistance- associated protein 3 plays an important role in protection against acute toxicity of diclofenac. Drug Metab Dispos 43:944–950CrossRefPubMedPubMedCentralGoogle Scholar
  300. Scott CA, Rajpopat S, Di WL (2013) Harlequin ichthyosis: ABCA12 mutations underlie defective lipid transport, reduced protease regulation and skin-barrier dysfunction. Cell Tissue Res 351:281–288CrossRefPubMedPubMedCentralGoogle Scholar
  301. Seeger RC, Brodeur GM, Sather H, Dalton A, Siegel SE, Wong KY et al (1985) Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med 313:1111–1116CrossRefPubMedPubMedCentralGoogle Scholar
  302. Seelheim P, Wüllner A, Galla HJ (2013) Substrate translocation and stimulated ATP hydrolysis of human ABC transporter MRP3 show positive cooperativity and are half-coupled. Biophys Chem 171:3–37CrossRefGoogle Scholar
  303. Semsei AF, Erdelyi DJ, Ungvari I, Csagoly E, Hegyi MZ, Kiszel PS et al (2012) ABCC1 polymorphisms in anthracycline-induced cardiotoxicity in childhood acute lymphoblastic leukaemia. Cell Biol Int 36:79–86CrossRefGoogle Scholar
  304. Seyffer F, Tampé R (2015) ABC transporters in adaptive immunity. Biochim Biophys Acta 1850:449–460CrossRefGoogle Scholar
  305. Shafran A, Ifergan I, Bram E, Jansen G, Kathmann I et al (2005) ABCG2 harboring the Gly482 mutation confers high-level resistance to various hydrophilic antifolates. Cancer Res 65:8414–8422CrossRefGoogle Scholar
  306. Shen S, Callaghan D, Juzwik C, Xiong H, Huang P, Zhang W (2010) ABCG2 reduces ROS-mediated toxicity and inflammation: a potential role in Alzheimer’s disease. J Neurochem 114:1590–1604CrossRefPubMedPubMedCentralGoogle Scholar
  307. Shord SS, Thompson DM, Krempl GA, Hanigan MH (2006) Effect of concurrent medications on cisplatin-induced nephrotoxicity in patients with head and neck cancer. Anti-Cancer Drugs 17:207–215CrossRefPubMedPubMedCentralGoogle Scholar
  308. Sicchieri RD, da Silveira WA, Raque L, Mandarano M, de Oliveira TMG, Carrara HHA et al (2015) ABCG2 is a potential marker of tumor-initiating cells in breast cancer. Tumor Biol 36:9233–9243CrossRefGoogle Scholar
  309. Siedlinski M, Boezen HM, Boer JM, Smit HA, Postma DS (2009) ABCC1 polymorphisms contribute to level and decline of lung function in two population-based cohorts. Pharmacogenet Genomics 19:675–684CrossRefPubMedPubMedCentralGoogle Scholar
  310. Siegsmund M, Brinkmann U, Scháffeler E, Weirich G, Schwab M, Eichelbaum et al (2002) Association of the P-glycoprotein transporter MDR1 (C3435T) polymorphism with the susceptibility to renal epithelial tumors. J Am Soc Nephrol 13:1847–1854CrossRefPubMedPubMedCentralGoogle Scholar
  311. Sigal N, Kaplan Zeevi M, Weinstein S, Peer D, Herskovits AA (2015) The human P-glycoprotein transporter enhances the type I interferon response to Listeria monocytogenes infection. Infect Immun 83:2358–2368CrossRefPubMedPubMedCentralGoogle Scholar
  312. Singh R, Srivastava A, Kapoor R, Mittal RD (2011) Do drug transporter(ABCB1) SNPs influence cyclosporine and tacrolimus dose requirements and renal allograft outcome in the posttransplantation period? J Clin Pharmacol 51:603–615CrossRefPubMedPubMedCentralGoogle Scholar
  313. Slot AJ, Molinski SV, Cole SP (2011) Mammalian multidrug-resistance proteins (MRPs). Essays Biochem 50:179–207CrossRefGoogle Scholar
  314. Slot AJ, Wise DD, Deeley RG, Monks TJ, Cole SP (2008) Modulation of human multidrug resistance protein (MRP) 1 (ABCC1) and MRP2 (ABCC2) transport activities by endogenous and exogenous glutathione-conjugated catechol metabolites. Drug Metab Dispos 36:552–560CrossRefPubMedPubMedCentralGoogle Scholar
  315. Smit JW, Huisman MT, van Tellingen O, Wiltshire HR, Schinkel AH (1999) Absence or pharmacological blocking of placental P-glycoprotein profoundly increases fetal drug exposure. J Clin Invest 104:1441–1447CrossRefPubMedPubMedCentralGoogle Scholar
  316. Solazzo M, Fantappiè O, Lasagna N, Sassoli C, Nosi D, Mazzanti R (2006) P-GP localization in mitochondria and its functional characterization in multiple drug-resistant cell lines. Exp Cell Res 312:4070–4078CrossRefPubMedPubMedCentralGoogle Scholar
  317. Solazzo M, Fantappie O, Amico MD, Sassoli C, Tani A, Cipriani G et al (2009) Mitochondrial expression and functional activity of breast cancer resistance protein in different multiple drug-resistant cell lines. Cancer Res 69:7235–7242CrossRefPubMedPubMedCentralGoogle Scholar
  318. Song S, Suzuki H, Kawai R, Sugiyama Y (1999) Effect of PSC 833, a P-glycoprotein modulator, on the disposition of vincristine and digoxin in rats. Drug Metab Dispos 27:689–694PubMedPubMedCentralGoogle Scholar
  319. Soroka CJ, Boyer JL (2014) Biosynthesis and trafficking of the bile salt export pump, BSEP: therapeutic implications of BSEP mutations. Mol Asp Med 37:3–14CrossRefGoogle Scholar
  320. Sparreboom A, van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DK et al (1997) Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci U S A 94:2031–2035CrossRefPubMedPubMedCentralGoogle Scholar
  321. Stapelbroek JM, van Erpecum KJ, Klomp LWJ, Houwen RHJ (2010) Liver disease associated with canalicular transport defects: Current and future therapies. J Hepatol 52:258–271CrossRefPubMedPubMedCentralGoogle Scholar
  322. Stephens RH, Tanianis-Hughes J, Higgs NB, Humphrey M, Warhurst G (2002) Region-dependent modulation of intestinal permeability by drug efflux transporters: in vitro studies in Mdr1a(−/−) mouse intestine. J Pharmacol Exp Ther 303:1095–1101CrossRefGoogle Scholar
  323. Surowiak P, Materna V, Kaplenko I, Spaczynski M, Dolinska-Krajewska B, Gebarowska E et al (2006) ABCC2 (MRP2, cMOAT) can be localized in the nuclear membrane of ovarian carcinomas and correlates with resistance to cisplatin and clinical outcome. Clin Cancer Res 12:7149–1458CrossRefPubMedPubMedCentralGoogle Scholar
  324. Tachibana T, Kitamura S, Kato M, Mitsui T, Shirasaka Y, Yamashita S et al (2010) Model analysis of the concentration-dependent permeability of P-GP substrates. Pharm Res 27:442–446CrossRefPubMedPubMedCentralGoogle Scholar
  325. Takada T, Ichida K, Matsuo H, Nakayama A, Murakami K, Yamanashi Y et al (2014) ABCG2 dysfunction increases serum uric acid by decreased intestinal urate excretion. Nucleosides Nucleotides Nucleic Acids 33:275–281CrossRefGoogle Scholar
  326. Takeichi T, Hsu CK, Yang HS, Chen HY, Wong TW, Tsai WL et al (2015) Progressive hyperpigmentation in a Taiwanese child due to an inborn error of vitamin B12 metabolism. Br J Dermatol 172:1111–1115CrossRefPubMedPubMedCentralGoogle Scholar
  327. Tamura A, Watanabe M, Saito H, Nakagawa H, Kamachi T, Okura et al (2006) Functional validation of the genetic polymorphisms of human ATP-binding cassette (ABC) transporter ABCG2: identification of alleles that are defective in porphyrin transport. Mol Pharmacol 70:287–296CrossRefPubMedPubMedCentralGoogle Scholar
  328. Tamura M, Kondo M, Horio M, Ando M, Saito H, Yamamoto M et al (2012) Genetic polymorphisms of the adenosine triphosphate-binding cassette transporters (ABCG2, ABCB1) and gefitinib toxicity. Nagoya J Med Sci 74:133–140PubMedPubMedCentralGoogle Scholar
  329. Tanabe M, Ieiri I, Nagata N, Inoue K, Ito S, Kanamori Y et al (2001) Expression of P-glycoprotein in human placenta: relation to genetic polymorphism of the multidrug resistance (MDR)-1 gene. J Pharmacol Exp Ther 297:1137–1143PubMedPubMedCentralGoogle Scholar
  330. Tanfin Z, Serrano-Sanchez M, Leiber D (2011) ATP-binding cassette ABCC1 is involved in the release of sphingosine 1-phosphate from rat uterine leiomyoma ELT3 cells and late pregnant rat myometrium. Cell Signal 23:1997–2004CrossRefPubMedPubMedCentralGoogle Scholar
  331. Tang K, Ngoi SM, Gwee PC, Chua JM, Lee EJ, Chong SS et al (2002) Distinct haplotype profiles and strong linkage disequilibrium at the MDR1 multidrug transporter gene locus in three ethnic Asian populations. Pharmacogenetics 12:437–450CrossRefPubMedPubMedCentralGoogle Scholar
  332. Tarling EJ, de Aguiar Vallim TQ, Edwards PA (2013) Role of ABC transporters in lipid transport and human disease. Trends Endocrinol Metab 24:342–350CrossRefPubMedPubMedCentralGoogle Scholar
  333. Tchernychev B, Ge P, Kessler MM, Solinga RM, Wachtel D, Tobin JV et al (2015) MRP4 modulation of the guanylate cyclase–C/cGMP pathway: effects on linaclotide-induced electrolyte secretion and cGMP efflux. J Pharmacol Exp Ther 355:48–56CrossRefPubMedPubMedCentralGoogle Scholar
  334. Temperilli F, Franco MD, Massimi I, Guarino ML, Guzzo MP, Valesini G et al (2016) Nonsteroidal anti-inflammatory drugs in-vitro and in-vivo treatment and multidrug resistance protein 4 expression in human platelets. Vasc Pharmacol 76:11–17CrossRefGoogle Scholar
  335. Thévenod F, Friedmann JM, Katsen AD, Hauser IA (2000) Up-regulation of multidrug resistance P-glycoprotein via nuclear factor-kappaB activation protects kidney proximal tubule cells from cadmium- and reactive oxygen species-induced apoptosis. Biol Chem 275:1887–1896CrossRefGoogle Scholar
  336. Thomas AC, Cullup T, Norgett EE, Hill T, Barton S, Dale BA et al (2006) ABCA12 is the major harlequin ichthyosis gene. J Invest Dermatol 126:2408–2413CrossRefPubMedPubMedCentralGoogle Scholar
  337. Tiribelli M, Fabbro D, Franzoni A, Fanin R, Damante G, Damiani D (2013) Q141K polymorphism of ABCG2 protein is associated with poor prognosis in adult acute myeloid leukemia treated with idarubicin-based chemotherapy. Haematologica 98:e28–e29CrossRefPubMedPubMedCentralGoogle Scholar
  338. Tiwari AK, Sodani K, Dai CL, Abuznait AH, Singh S, Xiao ZJ et al (2013) Nilotinib potentiates anticancer drug sensitivity in murine ABCB1-, ABCG2-, and ABCC10-multidrug resistance xenograft models. Cancer Lett 328:307–317CrossRefPubMedPubMedCentralGoogle Scholar
  339. Tomonari T, Takeishi S, Taniguchi T, Tanaka T, Tanaka H, Fujimoto S et al (2016) MRP3 as a novel resistance factor for sorafenib in hepatocellular carcinoma. Oncotarget 7: 7204–7217Google Scholar
  340. Toyoda Y, Ishikawa T (2010) Pharmacogenomics of Human ABC Transporter ABCC11 (MRP8): Potential Risk of Breast Cancer and Chemotherapy Failure Anticancer Agents. Med Chem 10:617–624Google Scholar
  341. Tsuruoka S, Sugimoto KI, Fujimura A, Imai M, Asano Y, Muto S (2001) P-glycoprotein-mediated drug secretion in mouse proximal tubule perfused in vitro. J Am Soc Nephrol 12:177–181PubMedPubMedCentralGoogle Scholar
  342. Tsybovsky Y, Molday RS, Palczewski K (2010) The ATP-binding cassette transporter ABCA4: structural and functional properties and role in retinal disease. Adv Exp Med Biol 703:105–125CrossRefPubMedPubMedCentralGoogle Scholar
  343. Uemura T, Oguri T, Ozasa H, Takakuwa O, Miyazaki M, Maeno K et al (2010) ABCC11/MRP8 confers pemetrexed resistance in lung cancer. Cancer Sci 101:2404–2410CrossRefPubMedPubMedCentralGoogle Scholar
  344. Ulrich DL, Lynch J, Wang Y, Fukuda Y, Nachagari D, Du G et al (2012) ATP-dependent mitochondrial porphyrin importer ABCB6 protects against phenylhydrazine toxicity. J Biol Chem 287:12679–12690CrossRefPubMedPubMedCentralGoogle Scholar
  345. Ushijima R, Takayama K, Izumi M, Harada T, Horiuchi Y, Uchino J et al (2007) Immunohistochemical expression of MRP2 and clinical resistance to platinum-based chemotherapy in small cell lung cancer. Anticancer Res 27:4351–4358PubMedPubMedCentralGoogle Scholar
  346. Vallakati A, Chandra PA, Pednekar M, Frankel R, Shani J (2013) Dronedarone- induced digoxin toxicity: new drug, new interactions. Am J Ther 20:e717–e719CrossRefPubMedPubMedCentralGoogle Scholar
  347. van Asperen J, van Tellingen O, Beijnen JH (2000) The role of mdr1a P-glycoprotein in the biliary and intestinal secretion of doxorubicin and vinblastine in mice. Drug Metab Dispos 28:264–267PubMedPubMedCentralGoogle Scholar
  348. van der Deen M, Marks H, Willemse BW, Postma DS, Müller M, Smit EF et al (2006) Diminished expression of multidrug resistance-associated protein 1 (MRP1) in bronchial epithelium of COPD patients. Virchows Arch 449:682–688CrossRefGoogle Scholar
  349. van Herwaarden AE, Jonker JW, Wagenaar E, Brinkhuis RF, Schellens JH, Beijnen JH et al (2003) The breast cancer resistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Cancer Res 63:6447–6452PubMedPubMedCentralGoogle Scholar
  350. van Herwaarden AE, Wagenaar E, Karnekamp B, Merino G, Jonker JW, Schinkel AH (2006) Breast cancer resistance protein (Bcrp1/Abcg2) reduces systemic exposure of the dietary carcinogens aflatoxin B1, IQ and Trp-P-1 but also mediates their secretion into breast milk. Carcinogenesis 27:123–130CrossRefPubMedPubMedCentralGoogle Scholar
  351. 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 89:1776–1782CrossRefPubMedPubMedCentralGoogle Scholar
  352. Vanwijngaerden YM, Wauters J, Langouche L, Vander Perre S, Liddle C, Setal C (2011) Critical illness evokes elevated circulating bile acids related to altered hepatic transporter and nuclear receptor expression. Hepatology 54:1741–1752CrossRefPubMedPubMedCentralGoogle Scholar
  353. Verstuyft C, Schwab M, Schaeffeler E, Kerb R, Brinkmann U, Jaillon P et al (2003) Digoxin pharmacokinetics and MDR1 genetic polymorphisms. Eur J Clin Pharmacol 58:809–812CrossRefPubMedPubMedCentralGoogle Scholar
  354. Vlaming ML, Mohrmann K, Wagenaar E, de Waart DR, Elferink RP, Lagas JS et al (2006) Carcinogen and anticancer drug transport by Mrp2 in vivo: study using Mrp2 (Abcc2) knockout mice. J Pharmacol Exp Ther 318:319–327CrossRefGoogle Scholar
  355. Vlaming ML, van Esch A, van de Steeg E, Pala Z, Wagenaar E, van Tellingen O et al (2011) Impact of Abcc2 [multidrug resistance-associated protein (mrp) 2], abcc3 (mrp3), and abcg2 (breast cancer resistance protein) on the oral pharmacokinetics of methotrexate and its main metabolite 7-hydroxymethotrexate. Drug Metabo Dispos 39:1338–1344CrossRefGoogle Scholar
  356. Volk EL, Schneider E (2003) Wild-Type Breast cancer resistance protein (BCRP/ABCG2) is a Methotrexate Polyglutamate Transporter. Cancer Res 63:5538–5543PubMedGoogle Scholar
  357. Vulsteke C, Pfeil AM, Maggen C, Schwenkglenks M, Pettengell R, Szucs et al (2015) Clinical and genetic risk factors for epirubicin-induced cardiac toxicity in early breast cancer patients. Breast Cancer Res Treat1 52:67–76CrossRefGoogle Scholar
  358. Walle UK, Walle T (1998) Taxol transport by human intestinal epithelial Caco-2 cells. Drug Metab Dispos 26:343–346PubMedPubMedCentralGoogle Scholar
  359. Wambach JA, Casey AM, Fishman MP, Wegner DJ, Wert SE, Cole FS et al (2014) Genotype-phenotype correlations for infants and children with ABCA3 deficiency. Am J Respir Crit Care Med 189:1538–1543CrossRefPubMedPubMedCentralGoogle Scholar
  360. Wang F, Zhou F, Kruh GD, Gallo JM (2010a) Influence of blood-brain barrier efflux pumps on the distribution of vincristine in brain and brain tumors. Neuro-Oncology 12:1043–1049CrossRefPubMedPubMedCentralGoogle Scholar
  361. Wang J, Zhang M, Zhang L, Cai H, Zhou S, Zhang J et al (2010b) Correlation of Nrf2, HO-1, and MRP3 in gallbladder cancer and their relationships to clinicopathologic features and survival. J Surg Res 164:199–105CrossRefGoogle Scholar
  362. Wang R, Chen HL, Liu L, Sheps JA, Phillips MJ, Ling V (2009) Compensatory role of P-glycoproteins in knockout mice lacking the bile salt export pump. Hepatology 50:948–956CrossRefPubMedPubMedCentralGoogle Scholar
  363. Wang YH, Chao PD, Hsiu SL, Wen KC, Hou YC (2004) Lethal quercetin-digoxin interaction in pig. Life Sci 74:1191–1197CrossRefPubMedPubMedCentralGoogle Scholar
  364. Weidner LD, Fung KL, Kannan P, Moen JK, Kumar JS, Mulder J et al (2016) Tariquidar is an inhibitor and not a substrate of human and mouse P-glycoprotein. Drug Metab Dispos 44:275–282CrossRefPubMedPubMedCentralGoogle Scholar
  365. Wen X, Buckley B, McCandlish E, Goedken MJ, Syed S, Pelis R et al (2014) Transgenic expression of the human MRP2 transporter reduces cisplatin accumulation and nephrotoxicity in Mrp2-null mice. Am J Pathol 184:1299–1308CrossRefPubMedPubMedCentralGoogle Scholar
  366. Wen J, Luo J, Huang W, Tang J, Zhou H, Zhang W (2015) The pharmacological and physiological roles of multidrug-resistant protein 4. J Pharmacol Exp Ther 354:358–375CrossRefPubMedPubMedCentralGoogle Scholar
  367. Wetterich U, Spahn-Langguth H, Mutschler E, Terhaag B, Rösch W, Langguth P (1996) Evidence for intestinal secretion as an additional clearance pathway of talinolol enantiomers: concentration- and dose-dependent absorption in vitro and in vivo. Pharm Res 13:514–552CrossRefPubMedPubMedCentralGoogle Scholar
  368. Widder JD, Guzik TJ, Mueller CF, Clempus RE, Schmidt HH, Dikalov SI et al (2007) Role of the multidrug resistance protein-1 in hypertension and vascular dysfunction caused by angiotensin II. Arterioscler Thromb Vasc Biol 27:762–768CrossRefPubMedPubMedCentralGoogle Scholar
  369. Wijnholds J, Scheffer GL, van der Valk M, van der Valk P, Beijnen JH, Scheper RJ et al (1998) Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage. J Exp Med 188:797–808CrossRefPubMedPubMedCentralGoogle Scholar
  370. Wijnholds J, deLange EC, Scheffer GL, van den Berg DJ, Mol CA, van der Valk M et al (2000) Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier. J Clin Invest 105:279–285CrossRefPubMedPubMedCentralGoogle Scholar
  371. Woodward OM, A Köttgen A, Köttgen M (2011) ABCG transporters and disease. FEBS J 278:3215–3225CrossRefPubMedPubMedCentralGoogle Scholar
  372. Wu H, Liu Y, Kang H, Xiao Q, Yao W, Zhao H et al (2015) Genetic variations in ABCG2 gene predict beast carcinoma susceptibility and clinical outcomes after treatment with anthracycline-based chemotherapy. Biomed Res Int 2015:279109PubMedPubMedCentralGoogle Scholar
  373. Xiong H, Callaghan D, Jones A, Bai J, Rasquinha I, Smith C et al (2009) ABCG2 is upregulated in Alzheimer’s brain with cerebral amyloid angiopathy and may act as a gatekeeper at the blood-brain barrier for Abeta(1-40) peptides. J Neurosci 29:5463–5475CrossRefPubMedPubMedCentralGoogle Scholar
  374. Yamada A, Ishikawa T, Ota I, Kimura M, Shimizu D, Tanabe M et al (2013) High expression of ATP-binding cassette transporter ABCC11 in breast tumors is associated with aggressive subtypes and low disease-free survival. Breast Cancer Res Treat 137:773–782CrossRefPubMedPubMedCentralGoogle Scholar
  375. Yamasaki M, Makino T, Masuzawa T, Kurokawa Y, Miyata H, Takiguchi S et al (2011) Role of multidrug resistance protein 2 (MRP2) in chemoresistance and clinical outcome in oesophageal squamous cell carcinoma. Brit J cancer 104:707–713CrossRefPubMedPubMedCentralGoogle Scholar
  376. Yang G, Wang XJ, Huang LJ, Zhou YA, Tian F, Jin-Bo Zhao JB et al (2015) High ABCG4 Expression is associated with poor prognosis in non-small-cell lung cancer patients treated with cisplatin-based chemotherapy. PLoS One 10:e0135576CrossRefPubMedPubMedCentralGoogle Scholar
  377. Yoh K, Ishii G, Yokose T, Minegishi Y, Tsuta K, Goto K et al (2004) Breast cancer resistance protein impacts clinical outcome in platinum-based chemotherapy for advanced non-small cell lung cancer. Clin Cancer Res 10:1691–1697CrossRefPubMedPubMedCentralGoogle Scholar
  378. Yoshioka M, Sagara H, Takahashi F, Harada N, Nishio K, Mori A et al (2009) Role of multidrug resistance-associated protein 1 in the pathogenesis of allergic airway inflammation. Am J Physiol Lung Cell Mol Physiol 296:L30–L36CrossRefPubMedPubMedCentralGoogle Scholar
  379. Yoshikado T, Takada T, Yamamoto T, Yamaji H, Ito K et al (2011) Itraconazole-induced cholestasis: involvement of the inhibition of bile canalicular phospholipid translocator MDR3/ABCB4. Mol Pharmacol 79:241–250CrossRefPubMedPubMedCentralGoogle Scholar
  380. Yu S, Yu Y, Liu L, Wang X, Lu S, Liang Y et al (2010) Increased plasma exposures of five protoberberine alkaloids from Coptidis Rhizoma in streptozotocin-induced diabetic rats: is P-GP involved? Planta Med 76:876–881CrossRefPubMedPubMedCentralGoogle Scholar
  381. Yu XH, Qian K, Jiang N, Zheng XL, Cayabyab FS, Tang CK (2014) ABCG5/ABCG8 in cholesterol excretion and atherosclerosis. Clin Chim Acta 428:82–88CrossRefPubMedPubMedCentralGoogle Scholar
  382. Yuan Y, Yang Z, Miao X, Li D, Liu Z, Zou Q (2015) The clinical significance of FRAT1 and ABCG2 expression in pancreatic ductal adenocarcinoma. Tumor Biol 36:9961–9968CrossRefGoogle Scholar
  383. Yvan-Charvet L, Wang N, Tall AR (2010) The role of HDL, ABCA1 and ABCG1 transporters in cholesterol efflux and immune responses. Arterioscler Thromb Vasc Biol 30:139–143CrossRefPubMedPubMedCentralGoogle Scholar
  384. Zalups RK, Joshee L, Christy C, Bridges CC (2014) Novel Hg2+-induced nephropathy in rats and mice lacking mrp2: evidence of axial heterogeneity in the handling of Hg2+ along the proximal tubule. Toxicol Sci 142:250–260CrossRefPubMedPubMedCentralGoogle Scholar
  385. Zelcer N, Huisman MT, Reid G, Wielinga P, Breedveld P, Kuil A et al (2003) Evidence for two interacting ligand binding sites in human multidrug resistance protein 2 (ATP binding cassette C2). J Biol Chem 278:23538–23544CrossRefGoogle Scholar
  386. Zelcer N, van de Wetering K, de Waart R, Scheffer GL, Marschall HU, Wielinga PR et al (2006) Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides. J Hepatolo 44:768–775CrossRefGoogle Scholar
  387. Zelcer N, van de Wetering K, Hillebrand M, Sarton E, Kuil A, Wielinga PR et al (2005) Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. Proc Natl Acad Sci U S A 102:7274–7279CrossRefPubMedPubMedCentralGoogle Scholar
  388. Zelcer N, Saeki T, Reid G, Beijnen JH, Borst P (2001) Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem 276:46400–46407CrossRefPubMedPubMedCentralGoogle Scholar
  389. Zeng H, Liu G, Rea PA, Kruh GD (2000) Transport of amphipathic anions by human multidrug resistance protein 3. Cancer Res 60:4779–4784PubMedPubMedCentralGoogle Scholar
  390. Zimmermann C, van de Wetering K, van de Steeg E, Wagenaar E, Vens C, Schinkel AH (2008) Species-dependent transport and modulation properties of human and mouse multidrug resistance protein 2 (MRP2/Mrp2, ABCC2/Abcc2). Drug Metab Dispos 36:631–640CrossRefPubMedPubMedCentralGoogle Scholar
  391. Zhang J, Zhou F, Wu X, Zhang X, Chen Y, Zha BS et al (2012) Cellular pharmacokinetic mechanisms of adriamycin resistance and its modulation by 20(S)-ginsenoside Rh2 in MCF-7/Adr cells. Br J Pharmacol 165:120–134CrossRefPubMedPubMedCentralGoogle Scholar
  392. Zhang W, Deng J, Sunkara M, Morris AJ, Wang C, St Clair D et al (2015) Loss of multidrug resistance-associated protein 1 potentiates chronic doxorubicin-induced cardiac dysfunction in mice. J Pharmacol Exp Ther 355:280–287CrossRefPubMedPubMedCentralGoogle Scholar
  393. Zhao X, Guo Y, Yue W, Zhang L, Gu M, Wang Y (2014) ABCC4 is required for cell proliferation and tumorigenesis in non-small cell lung cancer. OncoTargets Ther 7:343–351Google Scholar
  394. Zhou S, Morris JJ, Barnes Y, Lan L, Schuetz JD, Sorrentino BP (2002) Bcrp1 gene expression is required for normal numbers of side population stem cells in mice, and confers relative protection to mitoxantrone in hematopoietic cells in vivo. Proc Natl Acad Sci U S A 99:12339–11244CrossRefPubMedPubMedCentralGoogle Scholar
  395. Zhou L, Schmidt K, Nelson FR, Zelesky V, Troutman MD, Feng B (2009) The effect of breast cancer resistance protein and P-glycoprotein on the brain penetration of flavopiridol, imatinib mesylate (Gleevec), prazosin, and 2-methoxy-3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)propanoic acid (PF-407288) in mice. Drug Metab Dispos 37:946–955CrossRefPubMedPubMedCentralGoogle Scholar
  396. Zhou S, Zong Y, Ney PA, Nair G, Stewart CF, Sorrentino BP (2005) Increased expression of the Abcg2 transporter during erythroid maturation plays a role in decreasing cellular protoporphyrin IX level. Blood 105:2571–2576CrossRefPubMedPubMedCentralGoogle Scholar
  397. Zollmann T, Moiset G, Tumulka F, Tampé R, Poolman B, Abele R (2015) Single liposome analysis of peptide translocation by the ABC transporter TAPL. Proc Natl Acad Sci U S A 112:2046–2051CrossRefPubMedPubMedCentralGoogle Scholar
  398. Zutz A, Gompf S, Schägger H, Tampé R (2009) Mitochondrial ABC proteins in health and disease. Biochim Biophys Acta 1787:681–690CrossRefPubMedPubMedCentralGoogle Scholar
  399. Zyss J, Béhin A, Couvert P, Bouhour F, Sassolas A, Kolev I et al (2012) Clinical and electrophysiological characteristics of neuropathy associated with Tangier disease. J Neurol 259:1222–1226CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.China Pharmaceutical UniversityNanjingChina

Personalised recommendations