The canalicular bile salt export pump BSEP (ABCB11) as a potential therapeutic target

Current Drug Targets

Volumn 12, Issue 5, 2011, Pages 661-670

  Stieger, Bruno ^a   Beuers, Ulrich ^b  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

ABC transporter; Bile formation; BSEP; Cholestasis; Drug; Liver injury

Indexed keywords

ABC TRANSPORTER; BILE SALT; BILE SALT EXPORT PUMP; BOSENTAN; CYCLOSPORIN; GLIBENCLAMIDE; MEMBRANE PROTEIN; MESSENGER RNA; NALTREXONE; RETINOID X RECEPTOR; RIFAMPICIN; RIFAMYCIN; SERTRALINE; TROGLITAZONE; UNCLASSIFIED DRUG; URSODEOXYCHOLIC ACID;

BILE; BILE ACID METABOLISM; CHOLESTATIC HEPATITIS; DRUG WITHDRAWAL; ENTEROHEPATIC CIRCULATION; GENE MUTATION; HUMAN; IMMUNOHISTOCHEMISTRY; INFUSION PUMP; LIVER CELL; LIVER DISEASE; LIVER TOXICITY; PROTEIN EXPRESSION; PRURITUS; QUALITY CONTROL; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SMALL INTESTINE;

ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; BILE ACIDS AND SALTS; BILE CANALICULI; CHOLESTASIS; ENTEROHEPATIC CIRCULATION; HUMANS; LIVER; LIVER DISEASES; MOLECULAR TARGETED THERAPY;

EID: 79953327348     PISSN: 13894501     EISSN: None     Source Type: Journal    
DOI: 10.2174/138945011795378496     Document Type: Review

References (156)

1. Esteller A. Physiology of bile secretion. World J Gastroenterol 2008; 14: 5641-5649.
2. Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 2003; 83: 633-671.
3. Russell DW. Fifty years of advances in bile acid synthesis and metabolism. J Lipid Res 2009; 50 Suppl: S120-5.
4. Hunt MC, Alexson SE. Novel functions of acyl-CoA thioesterases and acyltransferases as auxiliary enzymes in peroxisomal lipid metabolism. Prog Lipid Res 2008; 47: 405-21.
5. Hofmann AF, Hagey LR. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci 2008; 65: 2461-83.
6. Hofmann AF. Bile acids: trying to understand their chemistry and biology with the hope of helping patients. Hepatology 2009; 49: 1403-18.
7. Hofmann AF. The enterohepatic circulation of bile acids in mammals: form and functions. Front Biosci 2009; 14: 2584-98.
8. Dawson PA, Lan T, Rao A. Bile acid transporters. J Lipid Res 2009; 50: 2340-57.
9. th century. New York: Lea & Ferbiger; 1994. p. 267-88.
10. Meier PJ, Stieger B. Bile salt transporters. Annu Rev Physiol 2002; 64:635-61.
11. Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 2004; 126: 322-42.
12. Pauli-Magnus C, Stieger B, Meier Y, Kullak Ublick GA, Meier PJ. Enterohepatic transport of bile salts and genetics of cholestasis. J Hepatol 2005; 43: 342-57.
13. Krahenbuhl S, Talos C, Fischer S, Reichen J. Toxicity of bile acids on the electron transport chain of isolated rat liver mitochondria. Hepatology 1994; 19: 471-9.
14. Rust C, Wild N, Bernt C, Vennegeerts T, Wimmer R, Beuers U. Bile acid-induced apoptosis in hepatocytes is caspase-6-dependent. J Biol Chem 2009; 284: 2908-16.
15. Hagenbuch B, Dawson P. The sodium bile salt cotransport family SLC10. Pflugers Arch 2004; 447: 566-70.
16. Hagenbuch B, Meier PJ. Organic anion transporting polypeptides of the OATP/SLC21 family: Phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/ functional properties. Pflugers Arch 2004; 447: 653-65.
17. Hagenbuch B, Gui C. Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family. Xenobiotica 2008; 38: 778-801.
18. Stolz A, Takikawa H, Ookhtens M, Kaplowitz N. The role of cytoplasmic proteins in hepatic bile acid transport. Annu Rev Physiol 1989; 51: 161-76.
19. Agellon LB, Torchia EC. Intracellular transport of bile acids. Biochim Biophys Acta 2000; 1486: 198-209.
20. Stieger B, Meier Y, Meier PJ. The bile salt export pump. Pflugers Arch 2007; 453: 611-20.
21. Stieger B. Recent insights into the function and regulation of the bile salt export pump (ABCB11). Curr Opin Lipidol 2009; 20: 176-81.
22. Reichen J, Paumgartner G. Uptake of bile acids by perfused rat liver. Am J Physiol 1976; 231: 734-42.
23. Hofmann AF, Mysels KJ. Bile acid solubility and precipitation in vitro and in vivo: the role of conjugation, pH, and Ca2+ ions. J Lipid Res 1992; 33: 617-26.
24. Weinman SA, Maglova LM. Free concentrations of intracellular fluorescent anions determined by cytoplasmic dialysis of isolated hepatocytes. Am J Physiol 1994; 267: G922-31.
25. Setchell KD, Rodrigues CM, Clerici C, et al. Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei. Gastroenterology 1997; 112: 226-35.
26. Masyuk AI, LaRusso NF. Aquaporins in the hepatobiliary system. Hepatology 2006; 43 (2 Suppl 1): S75-81.
27. Geyer J, Wilke T, Petzinger E. The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships. Naunyn Schmiedebergs Arch Pharmacol 2006; 372: 413-31.
28. Alrefai WA, Gill RK. Bile acid transporters: structure, function, regulation and pathophysiological implications. Pharm Res 2007; 24: 1803-23.
29. Ho RH, Tirona RG, Leake BF, et al. Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology 2006; 130: 1793-806.
30. Eloranta JJ, Kullak-Ublick GA. The role of FXR in disorders of bile acid homeostasis. Physiology (Bethesda) 2008; 23: 286-95.
31. Anwer MS. Cellular regulation of hepatic bile acid transport in health and cholestasis. Hepatology 2004; 39: 581-90.
32. Kalliokoski A, Niemi M. Impact of OATP transporters on pharmacokinetics. Br J Pharmacol 2009; 158: 693-705.
33. Glavy JS, Wu SM, Wang PJ, Orr GA, Wolkoff AW. Down-regulation by extracellular ATP of rat hepatocyte organic anion transport is mediated by serine phosphorylation of oatp1. J Biol Chem 2000; 275: 1479-84.
34. Guo GL, Klaassen CD. Protein kinase C suppresses rat organic anion transporting polypeptide 1- and 2-mediated uptake. J Pharmacol Exp Ther 2001; 299: 551-7.
35. Stieger B, Fattinger K, Madon J, Kullak Ublick GA, Meier PJ. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology 2000; 118: 422-30.
36. Hayashi H, Takada T, Suzuki H, Onuki R, Hofmann AF, Sugiyama Y. Transport by vesicles of glycine- and taurine-conjugated bile salts and taurolithocholate 3-sulfate: a comparison of human BSEP with rat Bsep. Biochim Biophys Acta 2005; 1738: 54-62.
37. Gerloff T, Stieger B, Hagenbuch B, et al. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem 1998; 273: 10046-50.
38. Carlton VE, Harris BZ, Puffenberger EG, et al. Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. Nat Genet 2003; 34: 91-6.
39. Hirano M, Maeda K, Hayashi H, Kusuhara H, Sugiyama Y. Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. J Pharmacol Exp Ther 2005; 314: 876-82.
40. Lo Sasso G, Petruzzelli M, Moschetta A. A translational view on the biliary lipid secretory network. Biochim Biophys Acta 2008; 1781: 79-96.
41. Fiorucci S, Rizzo G, Donini A, Distrutti E, Santucci L. Targeting farnesoid X receptor for liver and metabolic disorders. Trends Mol Med 2007; 13: 298-309.
42. Wang YD, Chen WD, Moore DD, Huang W. FXR: a metabolic regulator and cell protector. Cell Res 2008; 18: 1087-95.
43. Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. Role of bile acids and bile Acid receptors in metabolic regulation. Physiol Rev 2009; 89: 147-91.
44. Del Bas JM, Ricketts ML, Vaque M, et al. Dietary procyanidins enhance transcriptional activity of bile acid-activated FXR in vitro and reduce triglyceridemia in vivo in a FXR-dependent manner. Mol Nutr Food Res 2009; 53: 805-14.
45. Mehlmann JF, Crawley ML, Lundquist JT, et al. Pyrrole[2,3-d]azepino compounds as agonists of the farnesoid X receptor (FXR). Bioorg Med Chem Lett 2009; 19: 5289-92.
46. Fiorucci S, Mencarelli A, Distrutti E, Palladino G, Cipriani S. Targetting farnesoid-X-receptor: from medicinal chemistry to disease treatment. Curr Med Chem 2010; 17: 139-59.
47. Lundquist JT, Harnish DC, Kim CY, et al. Improvement of Physiochemical Properties of the Tetrahydroazepinoindole Series of Farnesoid X Receptor (FXR) Agonists: Beneficial Modulation of Lipids in Primates. J Med Chem 2010; 53: 1774-87.
48. Mi LZ, Devarakonda S, Harp JM, et al. Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mol Cell 2003; 11: 1093-100.
49. Noe J, Hagenbuch B, Meier PJ, St-Pierre MV. Characterization of the mouse bile salt export pump overexpressed in the baculovirus system. Hepatology 2001; 33: 1223-31.
50. Beuers U. Drug Insight: mechanisms and sites of action of ursodeoxycholic acid in cholestasis. Nat Clin Pract Gastroenterol Hepatol 2006; 3: 318-28.
51. Smit JJ, Schinkel AH, Oude Elferink RP, et al. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 1993; 75: 451-62.
52. Oude Elferink RP, Paulusma CC. Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein). Pflugers Arch 2007; 453: 601-10.
53. Small DM. Role of ABC transporters in secretion of cholesterol from liver into bile. Proc Natl Acad Sci USA 2003; 100: 4-6.
54. Hazard SE, Patel SB. Sterolins ABCG5 and ABCG8: regulators of whole body dietary sterols. Pflugers Arch 2007; 453: 745-52.
55. Trauner M, Fickert P, Halilbasic E, Moustafa T. Lessons from the toxic bile concept for the pathogenesis and treatment of cholestatic liver diseases. Wien Med Wochenschr 2008; 158: 542-8.
56. Gerloff T, Meier PJ, Stieger B. Taurocholate induces preferential release of phosphatidylcholine from rat liver canalicular vesicles. Liver 1998; 18: 306-12.
57. van Erpecum KJ, Carey MC. Influence of bile salts on molecular interactions between sphingomyelin and cholesterol: relevance to bile formation and stability. Biochim Biophys Acta 1997; 1345: 269-82.
58. Nibbering CP, Carey MC. Sphingomyelins of rat liver: biliary enrichment with molecular species containing 16:0 fatty acids as compared to canalicular-enriched plasma membranes. J Membr Biol 1999; 167: 165-71.
59. Munro S. Lipid rafts: elusive or illusive? Cell 2003; 115: 377-88.
60. Rajendran L, Simons K. Lipid rafts and membrane dynamics. J Cell Sci 2005; 118: 1099-102.
61. Ismair MG, Hausler S, Stuermer CA, et al. ABC-transporters are localized in caveolin-1-positive and reggie-1-negative and reggie-2-negative microdomains of the canalicular membrane in rat hepatocytes. Hepatology 2009; 49: 1673-82.
62. Paulusma CC, Groen A, Kunne C, et al. Atp8b1 deficiency in mice reduces resistance of the canalicular membrane to hydrophobic bile salts and impairs bile salt transport. Hepatology 2006; 44: 195-204.
63. Folmer DE, Elferink RP, Paulusma CC. P4 ATPases - lipid flippases and their role in disease. Biochim Biophys Acta 2009; 1791: 628-35.
64. Cai SY, Gautam S, Nguyen T, Soroka CJ, Rahner C, Boyer JL. ATP8B1 deficiency disrupts the bile canalicular membrane bilayer structure in hepatocytes, but FXR expression and activity are maintained. Gastroenterology 2009; 136: 1060-9.
65. Nies AT, Keppler D. The apical conjugate efflux pump ABCC2 (MRP2). Pflugers Arch 2007; 453: 643-59.
66. Kusuhara H, Sugiyama Y. ATP-binding cassette, subfamily G (ABCG family). Pflugers Arch 2007; 453: 735-44.
67. Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis 2009; 4: 1.
68. Oude Elferink RP, Paulusma CC, Groen AK. Hepatocanalicular transport defects: pathophysiologic mechanisms of rare diseases. Gastroenterology 2006; 130: 908-25.
69. Strautnieks SS, Bull LN, Knisely AS, et al. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet 1998; 20: 233-8.
70. van Mil SW, van der Woerd WL, van der Brugge G, et al. Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11. Gastroenterology 2004; 127: 379-84.
71. Lam CW, Cheung KM, Tsui MS, Yan MS, Lee CY, Tong SF. A patient with novel ABCB11 gene mutations with phenotypic transition between BRIC2 and PFIC2. J Hepatol 2006; 44: 240-2.
72. Takahashi A, Hasegawa M, Sumazaki R, et al. Gradual improvement of liver function after administration of ursodeoxycholic acid in an infant with a novel ABCB11 gene mutation with phenotypic continuum between BRIC2 and PFIC2. Eur J Gastroenterol Hepatol 2007; 19: 942-6.
73. Jansen PLM, Strautnieks SS, Jacquemin E, et al. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology 1999; 117: 1370-9.
74. Strautnieks SS, Byrne JA, Pawlikowska L, et al. Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families. Gastroenterology 2008; 134: 1203-14.
75. Locher KP. Review. Structure and mechanism of ATP-binding cassette transporters. Philos Trans R Soc Lond B Biol Sci 2009; 364: 239-45.
76. Seeger MA, van Veen HW. Molecular basis of multidrug transport by ABC transporters. Biochim Biophys Acta 2009; 1794: 725-37.
77. Rees DC, Johnson E, Lewinson O. ABC transporters: the power to change. Nat Rev Mol Cell Biol 2009; 10: 218-27.
78. Chen HL, Liu YJ, Su YN, et al. Diagnosis of BSEP/ABCB11 mutations in Asian patients with cholestasis using denaturing high performance liquid chromatography. J Pediatr 2008; 153: 825-32.
79. Treepongkaruna S, Gaensan A, Pienvichit P, et al. Novel ABCB11 mutations in a Thai infant with progressive familial intrahepatic cholestasis. World J Gastroenterol 2009; 15: 4339-42.
80. Byrne JA, Strautnieks SS, Ihrke G, et al. Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing. Hepatology 2009; 49: 553-67.
81. Keitel V, Burdelski M, Vojnisek Z, Schmitt L, Haussinger D, Kubitz R. De novo bile salt transporter antibodies as a possible cause of recurrent graft failure after liver transplantation: a novel mechanism of cholestasis. Hepatology 2009; 50: 510-7.
82. Jara P, Hierro L, Martinez-Fernandez P, et al. Recurrence of bile salt export pump deficiency after liver transplantation. N Engl J Med 2009; 361: 1359-67.
83. Wang L, Soroka CJ, Boyer JL. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II. J Clin Invest 2002; 110: 965-72.
84. Lam P, Pearson CL, Soroka CJ, Xu S, Mennone A, Boyer JL. Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases. Am J Physiol 2007; 293: C1709-16.
85. Plass JR, Mol O, Heegsma J, et al. A progressive familial intrahepatic cholestasis type 2 mutation causes an unstable, temperature-sensitive bile salt export pump. J Hepatol 2004; 40: 24-30.
86. Hayashi H, Takada T, Suzuki H, Akita H, Sugiyama Y. Two common PFIC2 mutations are associated with the impaired membrane trafficking of BSEP/ABCB11. Hepatology 2005; 41: 916-24.
87. Noe J, Kullak-Ublick GA, Jochum W, et al. Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis. J Hepatol 2005; 43: 536-43.
88. Alnouti Y. Bile Acid sulfation: a pathway of bile acid elimination and detoxification. Toxicol Sci 2009; 108: 225-46.
89. Zollner G, Trauner M. Molecular mechanisms of cholestasis. Wien Med Wochenschr 2006; 156: 380-5.
90. Geier A, Wagner M, Dietrich CG, Trauner M. Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration. Biochim Biophys Acta 2007; 1773: 283-308.
91. Ballatori N, Li N, Fang F, Boyer JL, Christian WV, Hammond CL. OST alpha-OST beta: a key membrane transporter of bile acids and conjugated steroids. Front Biosci 2009; 14: 2829-44.
92. Knisely AS, Strautnieks SS, Meier Y, et al. Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency. Hepatology 2006; 44: 478-86.
93. Palmeira CM, Rolo AP. Mitochondrially-mediated toxicity of bile acids. Toxicology 2004; 203: 1-15.
94. Sokol RJ, Devereaux M, Dahl R, Gumpricht E. Let there be bile--understanding hepatic injury in cholestasis. J Pediatr Gastroenterol Nutr 2006; 43 Suppl 1: S4-9.
95. Atherford PA, Jankowski JA. Molecular biology of Barrett's cancer. Best Pract Res Clin Gastroenterol 2006; 20: 813-27.
96. Souza RF, Krishnan K, Spechler SJ. Acid, bile, and CDX: the ABCs of making Barrett's metaplasia. Am J Physiol 2008; 295:G211-8.
97. Bleibel W, Kim S, D'Silva K, Lemmer ER. Drug-induced liver injury: review article. Dig Dis Sci 2007; 52: 2463-71.
98. Schuster D, Laggner C, Langer T. Why drugs fail--a study on side effects in new chemical entities. Curr Pharm Des 2005; 11: 3545-59.
99. Smith DA, Schmid EF. Drug withdrawals and the lessons within. Curr Opin Drug Discov Dev 2006; 9: 38-46.
100. Meier Y, Cavallaro M, Roos M, et al. Incidence of drug-induced liver injury in medical inpatients. Eur J Clin Pharmacol 2005; 61: 135-43.
101. Byrne JA, Strautnieks SS, Mieli-Vergani G, Higgins CF, Linton KJ, Thompson RJ. The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology 2002; 123: 1649-58.
102. Noe J, Stieger B, Meier PJ. Functional expression of the canalicular bile salt export pump of human liver. Gastroenterology 2002; 123: 1659-66.
103. Treiber A, Schneiter R, Hausler S, Stieger B. Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos 2007; 35: 1400-7.
104. Fattinger K, Cattori V, Hagenbuch B, Meier PJ, Stieger B. Rifamycin SV and rifampicin exhibit differential inhibition of the hepatic rat organic anion transporting polypeptides, Oatp1 and Oatp2. Hepatology 2000; 32: 82-6.
105. Stieger B. Role of the bile salt export pump, BSEP, in acquired forms of cholestasis. Drug Metab Disp 2010; 42: 437-45.
106. Fouassier L, Kinnman N, Lefevre G, et al. Contribution of mrp2 in alterations of canalicular bile formation by the endothelin antagonist bosentan. J Hepatol 2002; 37: 184-91.
107. Meier PJ. Canalicular bile formation: beyond single transporter functions. J Hepatol 2002; 37: 272-3.
108. Mano Y, Usui T, Kamimura H. Effects of bosentan, an endothelin receptor antagonist, on bile salt export pump and multidrug resistance-associated protein 2. Biopharm Drug Dispos 2007; 28: 13-8.
109. Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol 2009; 15: 2049-66.
110. Pusl T, Beuers U. Intrahepatic cholestasis of pregnancy. Orphanet J Rare Dis 2007; 2: 26.
111. Hay JE. Liver disease in pregnancy. Hepatology 2008; 47: 1067-76.
112. Gonzales E, Davit-Spraul A, Baussan C, Buffet C, Maurice M, Jacquemin E. Liver diseases related to MDR3 (ABCB4) gene deficiency. Front Biosci 2009; 14: 4242-56.
113. Kreek MJ. Female sex steroids and cholestasis. Semin Liver Dis 1987; 7: 8-23.
114. Reyes H, Simon FR. Intrahepatic cholestasis of pregnancy: an estrogen-related disease. Semin Liver Dis 1993; 13: 289-301.
115. Laatikainen T, Karjalainen O. Excertion of progesterone metabolites in urine and bile of pregnant women with intrahepatic cholestasis. J Steroid Biochem 1973; 4: 641-8.
116. Meng LJ, Reyes H, Palma J, Hernandez I, Ribalta J, Sjovall J. Profiles of bile acids and progesterone metabolites in the urine and serum of women with intrahepatic cholestasis of pregnancy. J Hepatol 1997; 27: 346-57.
117. Reyes H, Sjovall J. Bile acids and progesterone metabolites in intrahepatic cholestasis of pregnancy. Ann Med 2000; 32: 94-106.
118. Lindberg MC. Hepatobiliary complications of oral contraceptives. J Gen Intern Med 1992; 7: 199-209.
119. Yamamoto Y, Moore R, Hess HA, et al. Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity. J Biol Chem 2006; 281: 16625-31.
120. Meyers M, Slikker W, Pascoe G, Vore M. Characterization of cholestasis induced by estradiol-17 beta-D-glucuronide in the rat. J Pharmacol Exp Ther 1980; 214: 87-93.
121. Vallejo M, Briz O, Serrano MA, Monte MJ, Marin JJ. Potential role of trans-inhibition of the bile salt export pump by progesterone metabolites in the etiopathogenesis of intrahepatic cholestasis of pregnancy. J Hepatol 2005; 44: 1150-7.
122. Huang L, Smit JW, Meijer DK, Vore M. Mrp2 is essential for estradiol-17beta(beta-D-glucuronide)-induced cholestasis in rats. Hepatology 2000; 32: 66-72.
123. Akita H, Suzuki H, Ito K, et al. Characterization of bile acid transport mediated by multidrug resistance associated protein 2 and bile salt export pump. Biochim Biophys Acta 2001; 1511: 7-16.
124. Takada T, Weiss HM, Kretz O, Gross G, Sugiyama Y. Hepatic transport of PKI166, an epidermal growth factor receptor kinase inhibitor of the pyrrolo-pyrimidine class, and its main metabolite, ACU154. Drug Metab Dispos 2004; 32: 1272-8.
125. Mottino AD, Cao J, Veggi LM, Crocenzi F, Roma MG, Vore M. Altered localization and activity of canalicular Mrp2 in estradiol-17beta-D-glucuronide-induced cholestasis. Hepatology 2002; 35: 1409-19.
126. Crocenzi FA, Mottino AD, Cao J, et al. Estradiol-17beta-D-glucuronide induces endocytic internalization of Bsep in rats. Am J Physiol 2003; 285: G449-59.
127. Roma MG, Crocenzi FA, Mottino AD. Dynamic localization of hepatocellular transporters in health and disease. World J Gastroenterol 2008; 14: 6786-801.
128. Crocenzi FA, Sanchez Pozzi EJ, Ruiz ML, et al. Ca(2+)-dependent protein kinase C isoforms are critical to estradiol 17beta-D-glucuronide-induced cholestasis in the rat. Hepatology 2008; 48: 1885-95.
129. Fattinger K, Funk C, Pantze M, et al. The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther 2001; 69: 223-31.
130. Masubuchi Y. Metabolic and non-metabolic factors determining troglitazone hepatotoxicity: a review. Drug Metab Pharmacokinet 2006; 21: 347-56.
131. Julie NL, Julie IM, Kende AI, Wilson GL. Mitochondrial dysfunction and delayed hepatotoxicity: another lesson from troglitazone. Diabetologia 2008; 51: 2108-16.
132. Preininger K, Stingl H, Englisch R, et al. Acute troglitazone action in isolated perfused rat liver. Br J Pharmacol 1999; 126: 372-8.
133. Funk C, Ponelle C, Scheuermann G, Pantze M. Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity: in vivo and in vitro interaction at the canalicular bile salt export pump (Bsep) in the rat. Mol Pharmacol 2001; 59: 627-35.
134. Stapelbroek JM, van Erpecum KJ, Klomp LW, Houwen RH. Liver disease associated with canalicular transport defects: current and future therapies. J Hepatol 2010; 52: 258-71.
135. Davit-Spraul A, Fabre M, Branchereau S, et al. ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): Phenotypic differences between PFIC1 and PFIC2 and natural history. Hepatology 2010; 51: 1645-55.
136. Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology 2002; 36: 525-31.
137. Beuers U, Bilzer M, Chittattu A, et al. Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver. Hepatology 2001; 33: 1206-16.
138. Dumont M, Jacquemin E, Erlinger S. Effect of ursodeoxycholic acid on the expression of the hepatocellular bile acid transproters (Ntcp and bsep) in rats with estrogen-induced cholestasis. J Ped Gastroenterol Nutr 2002; 35: 185-91.
139. Marschall HU, Wagner M, Zollner G, et al. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans. Gastroenterology 2005; 129: 476-85.
140. Dombrowski F, Stieger B, Beuers U. Tauroursodeoxycholic acid inserts the bile salt export pump into canalicular membranes of cholestatic rat liver. Lab Invest 2006; 86: 166-74.
141. Fickert P, Wagner M, Marschall HU, et al. 24-norUrsodeoxycholic acid is superior to ursodeoxycholic acid in the treatment of sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology 2006; 130: 465-81.
142. Kremer AE, Beuers U, Oude-Elferink RP, Pusl T. Pathogenesis and treatment of pruritus in cholestasis. Drugs 2008; 68: 2163-82.
143. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol 2009; 51: 237-67.
144. Tandon P, Rowe BH, Vandermeer B, Bain VG. The efficacy and safety of bile Acid binding agents, opioid antagonists, or rifampin in the treatment of cholestasis-associated pruritus. Am J Gastroenterol 2007; 102: 1528-36.
145. Makishima M, Okamoto AY, Repa JJ, et al. Identification of a nuclear receptor for bile acids. Science 1999; 284: 1362-5.
146. Parks DJ, Blanchard SG, Bledsoe RK, et al. Bile acids: natural ligands for an orphan nuclear receptor. Science 1999; 284: 1365-8.
147. Neimark E, Chen F, Li X, Shneider BL. Bile acid-induced negative feedback regulation of the human ileal bile acid transporter. Hepatology 2004; 40: 149-56.
148. Pellicciari R, Fiorucci S, Camaioni E, et al. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J Med Chem 2002; 45: 3569-72.
149. Zollner G, Trauner M. Nuclear receptors as therapeutic targets in cholestatic liver diseases. Br J Pharmacol 2009; 156: 7-27.
150. Liu Y, Binz J, Numerick MJ, et al. Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis. J Clin Invest 2003; 112: 1678-87.
151. Dhawan A, Mitry RR, Hughes RD. Hepatocyte transplantation for liver-based metabolic disorders. J Inherit Metab Dis 2006; 29: 431-5.
152. Waelzlein JH, Puppi J, Dhawan A. Hepatocyte transplantation for correction of inborn errors of metabolism. Curr Opin Nephrol Hypertens 2009; 18: 481-8.
153. Meier Y, Pauli-Magnus C, Zanger UM, et al. Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver. Hepatology 2006; 44: 62-74.
154. Hayashi H, Sugiyama Y. 4-phenylbutyrate enhances the cell surface expression and the transport capacity of wild-type and mutated bile salt export pumps. Hepatology 2007; 45: 1506-16.
155. Feillet F, Leonard JV. Alternative pathway therapy for urea cycle disorders. J Inherit Metab Dis 1998; 21 Suppl 1: 101-11.
156. Nagasaka H, Yorifuji T, Kobayashi K, et al. Favorable effect of 4-phenylacetate on liver functions attributable to enhanced bile salt export pump expression in ornithine transcarbamylase-deficient children. Mol Genet Metab 2010; 100: 123-8.