1. LyonsAS, PetrucelliRJ. Ancient civilizations. In: RawlsW(ed). Medicine: An Illustrated History, 2nd edn. New York: Harry N. Abrams, Inc; 1987: 59.

2. SellingerM, BoyerJL. Physiology of bile secretion and cholestasis. In: PopperH, SchaffnerF(eds). Progress in Liver Disease, 9th edn. Philadelphia: W.B. Saunders; 1990: 237.

3. BoyerJL. New concepts of mechanisms of hepatocyte bile formation. Physiol Rev1980;60:303.

4. BoyerJL. Bile formation and secretion. Compr Physiol2013;3:1035.

5. WagnerM, TraunerM. Excretion. In: RodesJ, BenhamouJ, BleiA, et al. (eds). Textbook of Hepatology: From Basic Science to Clinical Practice, 3rd edn. Oxford: Blackwell; 2007: 290.

6. HofmannAF. Bile acids. In: AriasIM(ed). The Liver: Biology and Pathobiology, 3rd edn. New York: Raven Press; 1994: 677.

7. RussellDW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem2003;72:137. CrossRef

8. SheferS, HauserS, MosbachEH. 7‐alpha‐hydroxylation of cholestanol by rat liver microsomes. J Lipid Res1968;9:328.

9. AxelsonM, SjovallJ. Potential bile acid precursors in plasma–possible indicators of biosynthetic pathways to cholic and chenodeoxycholic acids in man. J Steroid Biochem1990;36:631. CrossRef

10. Kullak‐UblickGA, PaumgartnerG, BerrF. Long‐term effects of cholecystectomy on bile acid metabolism. Hepatology1995;21:41.

11. KillenbergPG. Measurement and subcellular distribution of choloyl‐CoA synthetase and bile acid‐CoA:amino acid N‐acyltransferase activities in rat liver. J Lipid Res1978;19:24.

12. SjovallJ. Dietary glycine and taurine on bile acid conjugation in man; bile acids and steroids 75. Proc Soc Exp Biol Med1959;100:676. CrossRef

13. SetchellKD, DumaswalaR, ColomboC, et al.Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbladder bile. J Biol Chem1988;263:16637.

14. RossiSS, ConverseJL, HofmannAF. High pressure liquid chromatographic analysis of conjugated bile acids in human bile: simultaneous resolution of sulfated and unsulfated lithocholyl amidates and the common conjugated bile acids. J Lipid Res1987;28:589.

15. Oude ElferinkRP, GroenAK. Mechanisms of biliary lipid secretion and their role in lipid homeostasis. Semin Liver Dis2000;20:293. CrossRef

16. GroenAK, Oude ElferinkRP. Lipid transport into bile and role in bile formation. Curr Drug Targets Immune Endocr Metabol Disord2005;5:131. CrossRef

17. LaRussoNF. Proteins in bile: how they get there and what they do. Am J Physiol1984;247:G199.

18. BarbhuiyaMA, SahasrabuddheNA, PintoSM, et al.Comprehensive proteomic analysis of human bile. Proteomics2011;11:4443. CrossRef

19. Reynoso‐PazS, CoppelRL, MackayIR, et al.The immunobiology of bile and biliary epithelium. Hepatology1999;30:351.

20. RosenHR, WinklePJ, KendallBJ, et al.Biliary interleukin‐6 and tumor necrosis factor‐alpha in patients undergoing endoscopic retrograde cholangiopancreatography. Dig Dis Sci1997;42:1290. CrossRef

21. GourleyGR. Neonatal jaundice and disorders of bilirubin metabolism. In: SuchyFJ, SokolRJ, BalistreriWF(eds). Liver Disease in Children, 3rd edn. Cambridge: Cambridge University Press; 2007: 270. CrossRef

22. GrafJ. Canalicular bile salt‐independent bile formation: concepts and clues from electrolyte transport in rat liver. Am J Physiol1983;244:G233.

23. AlpiniG, LenziR, SarkoziL, et al.Biliary physiology in rats with bile ductular cell hyperplasia. J Clin Invest1988;81:569. CrossRef

24. Van DykeRW, StevensJE, ScharschmidtBF. Effects of ion substitution on bile acid‐dependent and ‐independent bile formation by rat liver. J Clin Invest1982;70:505. CrossRef

25. KlosC, PaumgartnerG, ReichenJ. Cation‐anion gap and choleretic properties of rat bile. Am J Physiol1979;236:E434.

26. WheelerHO, RamosOL. Determinants of the flow and composition of bile in the unanesthetized dog during constant infusions of sodium taurocholate. J Clin Invest1960;39:161. CrossRef

27. NybergB, SonnenfeldT, EinarssonK. Vasoactive intestinal peptide and secretin: effects of combined and separate intravenous infusions on bile secretion in man. Scand J Gastroenterol1991;26:109. CrossRef

28. RomanRM, FitzJG. Emerging roles of purinergic signaling in gastrointestinal epithelial secretion and hepatobiliary function. Gastroenterology1999;116:964. CrossRef

29. FeranchakAP, FitzJG. Purinergic receptors and hepatobiliary function. In: SchwiebertEM(ed). Current Topics in Membranes, 54th edn. San Diego, CA: Academic Press, Elsevier Science; 2003: 395.

30. FeranchakAP, FitzJG. Adenosine triphosphate release and purinergic regulation of cholangiocyte transport. Semin Liver Dis2002;22:251. CrossRef

31. FeranchakAP, FitzJG. Thinking outside the cell: the role of extracellular adenosine triphosphate in bile formation. Gastroenterology2007;133:1726. CrossRef

32. DranoffJA, OgawaM, KruglovEA, et al.Expression of P2Y nucleotide receptors and ectonucleotidases in quiescent and activated rat hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol2004;287:G417. CrossRef

33. NathansonMH, BurgstahlerAD, MennoneA, et al.Characterization of cytosolic Ca2+ signaling in rat bile duct epithelia. Am J Physiol1996;271:G86.

34. McGillJ, BasavappaS, ShimokuraGH, et al.Adenosine triphosphate activates ion permeabilities in biliary epithelial cells. Gastroenterology1994;107:236.

35. SchlenkerT, RomacJMJ, ShararaA, et al.Regulation of biliary secretion through apical purinergic receptors in cultured rat cholangiocytes. Am J Physiol1997;273:G1108.

36. NathansonMH, BurgstahlerAD, MasyukA, et al.Stimulation of ATP secretion in the liver by therapeutic bile acids. Biochem J2001;358:1. CrossRef

37. DuttaAK, WooK, DoctorRB, et al.Extracellular nucleotides stimulate Cl‐ currents in biliary epithelia through receptor‐mediated IP3 and Ca2+ release. Am J Physiol Gastrointest Liver Physiol2008;295:G1004. CrossRef

38. HaradaM, SakisakaS, TeradaK, et al.A mutation of the Wilson disease protein, ATP7B, is degraded in the proteasomes and forms protein aggregates. Gastroenterology2001;120:967. CrossRef

39. KumarR, NagubandiS, MattoxVR, et al.Enterohepatic physiology of 1,25‐dihydroxyvitamin D3. J Clin Invest1980;65:277. CrossRef

40. GumucioJJ, GuibertEE. Zonal transport and functional compartmentation of the liver acinus. In: TavoloniN, BerkPB(eds). Hepatic Transport and Bile Secretion, 1st edn. New York: Raven Press; 1993: 71.

41. WeibelER, StaubliW, GnagiHR, et al.Correlated morphometric and biochemical studies on the liver cell. I. Morphometric model, stereologic methods, and normal morphometric data for rat liver. J Cell Biol1969;42:68. CrossRef

42. OshioC, PhillipsMJ. Contractility of bile canaliculi: implications for liver function. Science1981;212:1041. CrossRef

43. WatanabeN, TsukadaN, SmithCR, et al.Motility of bile canaliculi in the living animal: implications for bile flow. J Cell Physiol1991;113:1069.

44. MiticLL, AndersonJM. Molecular architecture of tight junctions. Annu Rev Physiol1998;60:121. CrossRef

45. McCarthyKM, SkareIB, StankewichMC, et al.Occludin is a functional component of the tight junction. J Cell Sci1996;109:2287.

46. HardisonWG, le‐MolleE, GosinkE, et al.Function of rat hepatocyte tight junctions: studies with bile acid infusions. Am J Physiol1991;260:G167.

47. ScharschmidtBF, Van DykeRW. Mechanisms of hepatic electrolyte transport. Gastroenterology1983;85:1199.

48. BoyerJL, GrafJ, MeierPJ. Hepatic transport systems regulating pHi, cell volume, and bile secretion. Annu Rev Physiol1992;54:415. CrossRef

49. GoreskyCA, SchwabAJ, PangKS. Kinetic models of hepatic transport at the organ level. In: TavoloniN, BerkPB(eds). Hepatic Transport and Bile Secretion, 1st edn. New York: Raven Press; 1993: 11.

50. JonesAL, HradekGT, RentsonRH, et al.Autoradiographic evidence for hepatic lobular concentration of bile acid derivative. Am J Physiol1980;238:G233.

51. FitzJG. Cellular mechanisms of bile secretion. In: ZakimD, BoyerTD(eds). Hepatology, 3rd edn. Philadelphia: W.B. Saunders Company; 1996: 362.

52. BenedettiA, BassottiC, RapinoK, et al.A morphometric study of the epithelium lining the rat intrahepatic biliary tree. J Hepatol1996;24:335. CrossRef

53. MasyukAI, MasyukTV, SplinterPL, et al.Cholangiocyte cilia detect changes in luminal fluid flow and transmit them into intracellular Ca(2+) and cAMP signaling. Gastroenterology2006;131:911. CrossRef

54. AlpiniG, RobertsS, KuntzSM, et al.Morphological, molecular, and functional heterogeneity of cholangiocytes from normal rat liver. Gastroenterology1996;110:1636. CrossRef

55. MarzioniM, GlaserSS, FrancisH, et al.Functional heterogeneity of cholangiocytes. Semin Liver Dis2002;22:227. CrossRef

56. TavaloniN. The intrahepatic biliary epithelim: an area of growing interest in hepatology. Semin Liver Dis1987;7:280. CrossRef

57. KumarU, JordanTW. Isolation and culture of biliary epithelial cells from the biliary tract fraction of normal rats. Liver1986;6:369. CrossRef

58. NathansonMH, BoyerJL. Mechanisms and regulation of bile secretion. Hepatology1991;14:551. CrossRef

59. McGillJ, GettysTW, BasavappaS, et al.Secretin activates Cl‐ channels in bile duct epithelial cells through a cAMP‐dependent mechanism. Am J Physiol1994;266:G731.

60. AlpiniG, GlaserS, RobertsonW, et al.Large but not small intrahepatic bile ducts are involved in secretin‐regulated ductal bile secretion. Am J Physiol1997;272:G1064.

61. GlaserS, FrancisH, DemorrowS, et al.Heterogeneity of the intrahepatic biliary epithelium. World J Gastroenterol2006;12:3523.

62. FrancisH, GlaserS, DemorrowS, et al.Small mouse cholangiocytes proliferate in response to H1 histamine receptor stimulation by activation of the IP3/CaMK I/CREB pathway. Am J Physiol Cell Physiol2008;295:C499. CrossRef

63. WooK, SatheM, KresgeC, et al.Adenosine triphosphate release and purinergic (P2) receptor‐mediated secretion in small and large mouse cholangiocytes. Hepatology2010;52:1819. CrossRef

64. HofmannAF. Bile acids: the good, the bad, and the ugly. News Physiol Sci1999;14:24.

65. Kullak‐UblickGA, StiegerB, HagenbuchB, et al.Hepatic transport of bile salts. Semin Liver Dis2000;20:273. CrossRef

66. GongYZ, EverettET, SchwartzDA, et al.Molecular cloning, tissue distribution, and expression of a 14‐kDa bile acid‐binding protein from rat ileal cytosol. Proc Natl Acad Sci U S A1994;91:4741. CrossRef

67. DawsonPA, HubbertM, HaywoodJ, et al.The heteromeric organic solute transporter alpha‐beta, Ostalpha‐Ostbeta, is an ileal basolateral bile acid transporter. J Biol Chem2005;280:6960. CrossRef

68. BallatoriN, ChristianWV, LeeJY, et al.OSTalpha‐OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia. Hepatology2005;42:1270. CrossRef

69. PriesJM, ShermanCA, WilliamsGC, et al.Hepatic extraction of bile salts in conscious dog. Am J Physiol1979;236:E191.

70. HofmannAF. Current concepts of biliary secretion. Dig Dis Sci1989;34(12 Suppl):16S. CrossRef

71. LazaridisKN, PhamL, TietzP, et al.Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium‐dependent bile acid transporter. J Clin Invest1997;100:2714. CrossRef

72. AlpiniG, GlaserSS, RodgersR, et al.Functional expression of the apical Na+‐dependent bile acid transporter in large but not small rat cholangiocytes. Gastroenterology1997;113:1734. CrossRef

73. LazaridisKN, TietzP, WuT, et al.Alternative splicing of the rat sodium/bile acid transporter changes its cellular localization and transport properties. Proc Natl Acad Sci U S A2000;97:11092. CrossRef

74. XiaX, FrancisH, GlaserS, et al.Bile acid interactions with cholangiocytes. World J Gastroenterol2006;12:3553.

75. YoonYB, HageyLR, HofmannAF, et al.Effect of side chain shortening on the physiologic properties of bile acids: hepatic transport and effect on biliary secretion of 23‐Nor‐ursodeoxycholate in rodents. Gastroenterology1986;90:837.

76. BrauerRW, LeongGF, HollowayRJ. Mechanics of bile secretion; effect of perfusion pressure and temperature on bile flow and bile secretion pressure. Am J Physiol1954;177:103.

77. SperberI. Secretion of organic anions in the formation of urine and bile. Pharmacol Rev1959;11:109.

78. BoyerJL. Bile formation and Cholestasis. In: SchiffER, SorrellMF, MaddreyWC(eds). Schiff's Diseases of the Liver. Philadelphia: Lippincott, Williams & Wilkins; 2002: 135.

79. PreisigR, CooperHL, WheelerHO. The relationship between taurocholate secretion rate and bile production in the unanesthetized dog during cholinergic blockade and during secretin administration. J Clin Invest1962;41:1152. CrossRef

80. GurantzD, HofmannAF. Influence of bile acid structure on bile flow and biliary lipid secretion in the hamster. Am J Physiol1984;247:G736.

81. ThomsenOO, LarsenJA. Interaction of insulin, glucagon, and DBcAMP on bile acid‐independent bile production in the rat. Scand J Gastroenterol1982;17:687. CrossRef

82. HofmannAF, HageyLR. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci2008;65:2461. CrossRef

83. ScharschmidtBF, StephensJE. Transport of sodium, chloride, and taurocholate by cultured rat hepatocytes. Proc Natl Acad Sci U S A1981;78:986. CrossRef

84. FitzJG. Na+‐coupled solute transport in hepatocytes. In: TavoloniN, BerkPB(eds). Hepatic Transport and Bile Secretion, 1st edn. New York: Raven Press; 1993: 281.

85. SztulES, BiemesderferD, CaplanMJ, et al.Localization of Na+,K+‐ATPase alpha‐subunit to the sinusoidal and lateral but not canalicular membranes of rat hepatocytes. J Cell Biol1987;104:1239. CrossRef

86. Van DykeRW, ScharschmidtBF. (Na,K)‐ATPase mediated cation pumping in cultured rat hepatocytes. J Biol Chem1983;258:12912.

87. FitzJG, ScharschmidtBF. Regulation of transmembrane electrical potential difference in rat hepatocytes in situ. Am J Physiol1987;252:G56.

88. FitzJG, LidofskySD, XieMH, et al.Transmembrane electrical potential difference regulates Na+/HCO3‐ cotransport and intracellular pH in hepatocytes. Proc Natl Acad Sci U S A1992;89:4197. CrossRef

89. FitzJG, LidofskySD, ScharschmidtBF. Regulation of hepatic Na+/HCO3‐ cotransport and pH by membrane potential difference. Am J Physiol1993;265:G1.

90. WeinmanSA, GrafJ, BoyerJL. Voltage‐drive, taurocholate‐dependent secretion in isolated rat hepatocyte couplets. Am J Physiol1989;256:G826.

91. FitzJG, LidofskySD, WeisigerRA, et al.HCO3‐coupled Na+ influx is a major determinant of Na+ turnover and Na+/K+ pump activity in rat hepatocytes. J Membr Biol1991;122:1. CrossRef

92. LondonCD, DiamondJM, BrooksFP. Electrical potential differences in the biliary tree. Biochim Biophys Acta1968;150:509. CrossRef

93. FitzJG. Regulation of cholangiocyte secretion. Semin Liver Dis2002;22:241. CrossRef

94. SinghSK, MennoneA, GigliozziA, et al.Cl(‐)‐dependent secretory mechanisms in isolated rat bile duct epithelial units. Am J Physiol Gastrointest Liver Physiol2001;281:G438.

95. FitzJG, BasavappaS, McGillJ, et al.Regulation of membrane chloride currents in rat bile duct epithelial cells. J Clin Invest1993;91:319. CrossRef

96. RomanRM, FeranchakAP, SalterKD, et al.Endogenous ATP regulates Cl‐ secretion in cultured human and rat biliary epithelial cells. Am J Physiol1999;276:G1391.

97. SalterKD, FitzJG, RomanRM. Domain‐specific purinergic signaling in polarized rat cholangiocytes. Am J Physiol Gastrointest Liver Physiol2000;278:G492.

98. AlvaroD, ChoWK, MennoneA, et al.Effect of secretin on intracellular pH regulation in isolated rat bile duct epithelial cells. J Clin Invest1993;92:1314. CrossRef

99. BruckR, HaddadP, GrafJ, et al.Regulatory volume decrease stimulates bile flow, bile acid excretion, and exocytosis in isolated perfused rat liver. Am J Physiol1992;262:G806.

100. RomanRM, WangY, LidofskySD, et al.Hepatocellular ATP‐binding cassette protein expression enhances ATP release and autocrine regulation of cell volume. J Biol Chem1997;272:21970. CrossRef

101. DranoffJA, NathansonMH. It's swell to have ATP in the liver. J Hepatol2000;33:323. CrossRef

102. FeranchakAP, FitzJG, RomanRM. Volume‐sensitive purinergic signaling in human hepatocytes. J Hepatol2000;33:174. CrossRef

103. LidofskySD, RomanRM. Alanine uptake activates hepatocellular chloride channels. Am J Physiol1997;273:G849.

104. WangY, RomanRM, LidofskySD, et al.Autocrine signaling through ATP release represents a novel mechanism for cell volume regulation. Proc Natl Acad Sci U S A1996;93:12020. CrossRef

105. ReinhartPH, ChungS, LevitanIB. A family of calcium‐dependent potassium channels from rat brain. Neuron1989;2:1031. CrossRef

106. HaussingerD. Regulation and functional significance of liver cell volume. In: BoyerJL, OcknerRK(eds). Progress in Liver Disease, 14th edn. Philadelphia: W.B. Saunders; 1996: 29.

107. HaussingerD, HallbruckerC, SahaN, et al.Cell volume and bile acid excretion. Biochem J1992;288:681. CrossRef

108. HaussingerD, LangF, GerokW. Regulation of cell function by the cellular hydration state. Am J Physiol1994;267:E343.

109. DunkelbergJC, FeranchakAP, FitzJG. Liver cell volume regulation: size matters. Hepatology2001;33:1349. CrossRef

110. PalmerR, GurantzD, HofmannAF, et al.Hypercholeresis induced by norchenodeoxycholate in biliary fistula rodent. Am J Physiol1987;252:G219.

111. LakeJR, RennerER, ScharschmidtBF, et al.Bile acid induced bile flow and bile acid transformation. Inhibition of ursodeoxycholate‐stimulated hypercholeresis in the rat by sodium substitution, amiloride, or amiloride analogs is associated with replacement of biliary unconjugated ursodeoxycholate by its glucuronide. Gastroenterology1988;95:454.

112. SmitJJM, SchinkelAH, Oude ElferinkRPJ, et al.Homozygous disruption of the murine mdr2 P‐glycoprotein gene leads to complete absence of phospholipid from bile and to liver disease. Cell1993;75:451. CrossRef

113. HagenbuchB, SteigerB, FoguetM, et al.Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc Natl Acad Sci U S A1991;88:10629. CrossRef

114. StiegerB, HagenbuchB, LandmannL, et al.In situ localization of the hepatocytic Na+/taurocholate cotransporting polypeptide in rat liver. Gastroenterology1994;107:1781.

115. HagenbuchB, MeierPJ. Molecular cloning, chromosomal localization, and functional characterization of a human Na+/bile acid cotransporter. J Clin Invest1994;93:1326. CrossRef

116. WeinmanSA, CarruthMW, DawsonPA. Bile acid uptake via the human apical sodium‐bile acid cotransporter is electrogenic. J Biol Chem1998;273:34691. CrossRef

117. GruneS, MengXJ, WeinmanSA. cAMP stimulates fluorescent bile acid uptake into hepatocytes by membrane hyperpolarization. Am J Physiol1996;270:G339.

118. Kullak‐UblickGA, HagenbuchB, StiegerB, et al.Functional characterization of the basolateral rat liver organic anion transporting polypeptide. Hepatology1994;20:411.

119. SatlinLM, AminV, WolkoffAW. Organic anion transporting polypeptide mediates organic anion. J Biol Chem1997;272:26340. CrossRef

120. LiL, LeeTK, MeierPJ, et al.Identification of glutathione as a driving force and leukotriene C4 as a substrate for oatp1, the hepatic sinusoidal organic solute transporter. J Biol Chem1998;273:16184. CrossRef

121. BallatoriN, TruongAT. Relation between biliary glutathione excretion and bile acid‐independent bile flow. Am J Physiol1989;256:G22.

122. SekineT, ChaSH, EndouH. The multispecific organic anion transporter (OAT) family. Pflugers Arch2000;440:337. CrossRef

123. SweetDH, PritchardJB. The molecular biology of renal organic anion and organic cation transporters. Cell Biochem Biophys1999;31:89. CrossRef

124. BallatoriN. Biology of a novel organic solute and steroid transporter, OSTalpha‐OSTbeta. Exp Biol Med (Maywood)2005;230:689.

125. KonigJ, RostD, CuiY, et al.Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane. Hepatology1999;29:1156. CrossRef

126. ChenZS, LeeK, KruhGD. Transport of cyclic nucleotides and estradiol 17‐beta‐D‐glucuronide by multidrug resistance protein 4. Resistance to 6‐mercaptopurine and 6‐thioguanine. J Biol Chem2001;276:33747. CrossRef

127. KepplerD. Multidrug resistance proteins (MRPs, ABCCs): importance for pathophysiology and drug therapy. Handb Exp Pharmacol2011;201:299. CrossRef

128. ZollnerG, WagnerM, FickertP, et al.Expression of bile acid synthesis and detoxification enzymes and the alternative bile acid efflux pump MRP4 in patients with primary biliary cirrhosis. Liver Int2007;27:920. CrossRef

129. ZollnerG, FickertP, SilbertD, et al.Adaptive changes in hepatobiliary transporter expression in primary biliary cirrhosis. J Hepatol2003;38:717. CrossRef

130. ErlingerS. Intracellular events in bile acid transport by the liver. In: TavoloniN, BerkPB(eds). Hepatic Transport and Bile Secretion, 1st edn. New York: Raven Press; 1993: 467.

131. KitamuraT, GatmaitanZ, AriasIM. Serial quantitative image analysis and confocal microscopy of hepatic uptake, intracellular distribution and biliary secretion of a fluorescent bile acid analog in rat hepatocyte doublets. Hepatology1990;12:1358. CrossRef

132. StolzA, HammondL, LouH. Rat and human bile acid binders are members of the monomeric reductase gene family. Adv Exp Med Biol1995;372:269. CrossRef

133. SugiyamaY, StolzA, SugimotoM, et al.Evidence for a common high affinity binding site on glutathione S‐transferase B for lithocholic acid and bilirubin. J Lipid Res1984;25:1177.

134. CrawfordJM, BerkenCA, GollanJL. Role of the hepatocyte microtubular system in the excretion of bile salts and biliary lipid: implications for intracellular vesicular transport. J Lipid Res1988;29:144.

135. ScharschmidtBF, LakeJR, RennerER, et al.Fluid phase endocytosis by cultured rat hepatocytes and perfused rat liver: implications for plasma membrane turnover and vesicular trafficking of fluid phase markers. Proc Natl Acad Sci U S A1986;83:9488. CrossRef

136. StorchJ, ThumserAE. The fatty acid transport function of fatty acid‐binding proteins. Biochim Biophys Acta2000;1486:28. CrossRef

137. GerloffT, SteigerB, HagenbuchB, et al.The sister of P‐glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem1998;273:10046. CrossRef

138. StrautnieksSS, BullLN, KniselyAS, et al.A gene encoding a liver‐specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet1998;20:233. CrossRef

139. NoeJ, StiegerB, MeierPJ. Functional expression of the canalicular bile salt export pump of human liver. Gastroenterology2002;123:1659. CrossRef

140. JansenPL, StrautnieksSS, JacqueminE, et al.Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology1999;117:1370. CrossRef

141. NishidaT, GatmaitanZ, CheM, et al.Rat liver canalicular membrane vesicles contain an ATP‐dependent bile acid transport system. Proc Natl Acad Sci U S A1991;88:6590. CrossRef

142. ChenHL, ChenHL, LiuYJ, et al.Developmental expression of canalicular transporter genes in human liver. J Hepatol2005;43:472. CrossRef

143. RuetzS, GrosP. Phosphatidylcholine translocase: a physiological role for the mdr2 gene. Cell1994;77:1071. CrossRef

144. SmitJJ, SchinkelAH, MolCA, et al.Tissue distribution of the human MDR3 P‐glycoprotein. Lab Invest1994;71:638.

145. SmithAJ, de VreeJM, OttenhoffR, et al.Hepatocyte‐specific expression of the human MDR3 P‐glycoprotein gene restores the biliary phosphatidylcholine excretion absent in Mdr2 (‐/‐) mice. Hepatology1998;28:530. CrossRef

146. PaulusmaCC, Oude ElferinkRP. The type 4 subfamily of P‐type ATPases, putative aminophospholipid translocases with a role in human disease. Biochim Biophys Acta2005;1741:11. CrossRef

147. UjhazyP, OrtizD, MisraS, et al.Familial intrahepatic cholestasis 1: studies of localization and function. Hepatology2001;34:768. CrossRef

148. CaiSY, GautamS, NguyenT, et al.ATP8B1 deficiency disrupts the bile canalicular membrane bilayer structure in hepatocytes, but FXR expression and activity are maintained. Gastroenterology2009;136:1060. CrossRef

149. PaulusmaCC, de WaartDR, KunneC, et al.Activity of the bile salt export pump (ABCB11) is critically dependent on canalicular membrane cholesterol content. J Biol Chem2009;284:9947. CrossRef

150. ChenF, AnanthanarayananM, EmreS, et al.Progressive familial intrahepatic cholestasis, type 1, is associated with decreased farnesoid X receptor activity. Gastroenterology2004;126:756. CrossRef

151. VerhulstPM, van der VeldenLM, OorschotV, et al.A flippase‐independent function of ATP8B1, the protein affected in familial intrahepatic cholestasis type 1, is required for apical protein expression and microvillus formation in polarized epithelial cells. Hepatology2010;51:2049. CrossRef

152. BergeKE, TianH, GrafGA, et al.Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science2000;290:1771. CrossRef

153. GrafGA, YuL, LiWP, et al.ABCG5 and ABCG8 are obligate heterodimers for protein trafficking and biliary cholesterol excretion. J Biol Chem2003;278:48275. CrossRef

154. KlettEL, PatelS. Genetic defenses against noncholesterol sterols. Curr Opin Lipidol2003;14:341. CrossRef

155. GatmaitanZC, AriasIM. Structure and function of P‐glycoprotein in normal liver and small intestine. Adv Pharmacol1993;24:77. CrossRef

156. AmbudkarSV, DeyS, HrycynaCA, et al.Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol1999;39:361. CrossRef

157. ThiebautF, TsuruoT, HamadaH, et al.Cellular localization of the multidrug‐resistance gene product P‐glycoprotein in normal human tissues. Proc Natl Acad Sci U S A1987;84:7735. CrossRef

158. LamP, WangR, LingV. Bile acid transport in sister of P‐glycoprotein (ABCB11) knockout mice. Biochemistry2005;44:12598. CrossRef

159. NiZ, BikadiZ, RosenbergMF, et al.Structure and function of the human breast cancer resistance protein (BCRP/ABCG2). Curr Drug Metab2010;11:603. CrossRef

160. AndoT, KusuharaH, MerinoG, et al.Involvement of breast cancer resistance protein (ABCG2) in the biliary excretion mechanism of fluoroquinolones. Drug Metab Dispos2007;35:1873. CrossRef

161. KeitelV, NiesAT, BromM, et al.A common Dubin‐Johnson syndrome mutation impairs protein maturation and transport activity of MRP2 (ABCC2). Am J Physiol Gastrointest Liver Physiol2003;284:G165. CrossRef

162. ThomsenOO, LarsenJA. The effect of glucagon, dibutyrylic cyclic AMP and insulin on bile production in the intact rat and the perfused rat liver. Scand J Gastroenterol1981;111:23.

163. BallatoriN, JacobR, BoyerJL. Intrabiliary glutathione hydrolysis. J Biol Chem1986;261:7860.

164. BallatoriN, TruongAT, MaAK, et al.Determinants of glutathione efflux and biliary GSH/GSSG ratio in perfused rat liver. Am J Physiol1989;256:G482.

165. DietrichCG, OttenhoffR, de WaartDR, et al.Role of MRP2 and GSH in intrahepatic cycling of toxins. Toxicology2001;167:73. CrossRef

166. HardisonWGM, WoodCA. Importance of HCO3‐ in bile salt‐independent fraction of bile flow. Am J Physiol1978;235:E158.

167. MoseleyRH, MeierPJ, AronsonPS, et al.Na‐H exchange in rat liver basolateral but not canalicular plasma membrane vesicles. Am J Physiol1986;250:G35.

168. HendersonRM, GrafJ, BoyerJL. Na‐H exchange regulates intracellular pH in isolated rat hepatocyte couplets. Am J Physiol1987;252:G109.

169. GleesonD, SmithND, BoyerJL. Bicarbonate dependent and independent pH regulatory mechanisms in rat hepatocytes. J Clin Invest1989;84:312. CrossRef

170. RennerER, LakeJR, ScharschmidtBF, et al.Rat hepatocytes exhibit basolateral Na+/HCO3 cotransport. J Clin Invest1989;83:1225. CrossRef

171. MeierPJ, KnickelbeinR, MoseleyRH, et al.Evidence of carrier‐mediated chloride/bicarbonate exchange in canalicular rat liver plasma membrane vesicles. J Clin Invest1985;75:1256. CrossRef

172. BenedettiA, StrazzaboscoM, CorasantiJG, et al.Cl‐/HCO3‐ exchanger in isolated rat hepatocytes: role in regulation of intracellular pH. Am J Physiol1991;261:G512.

173. RomanRM, SmithRL, FeranchakAP, et al.ClC‐2 chloride channels contribute to HTC cell volume homeostasis. Am J Physiol Gastrointest Liver Physiol2001;280:G344.

174. ShimadaK, LiX, XuG, et al.Expression and canalicular localization of two isoforms of the ClC‐3 chloride channel from rat hepatocytes. Am J Physiol Gastrointest Liver Physiol2000;279:G268.

175. MarinelliRA, LaRussoNF. Aquaporin water channels in liver: their significance in bile formation. Hepatology1997;26:1081. CrossRef

176. MarinelliRA, TietzPS, CarideAJ, et al.Water transporting properties of hepatocyte basolateral and canalicular plasma membrane domains. J Biol Chem2003;278:43157. CrossRef

177. CarrerasFI, GradiloneSA, MazzoneA, et al.Rat hepatocyte aquaporin‐8 water channels are down‐regulated in extrahepatic cholestasis. Hepatology2003;37:1026. CrossRef

178. GradiloneSA, GarciaF, HuebertRC, et al.Glucagon induces the plasma membrane insertion of functional aquaporin‐8 water channels in isolated rat hepatocytes. Hepatology2003;37:1435. CrossRef

179. HugentoblerG, MeierPJ. Multispecific anion exchange in basolateral (sinusoidal) rat liver plasma membrane vesicles. Am J Physiol1986;252:G656.

180. BruckR, BenedettiA, StrazzaboscoM, et al.Intracellular alkalinization stimulates bile flow and vesicular‐mediated exocytosis in IPRL. Am J Physiol1993;265:G347.

181. Martinez‐AnsoE, CastilloJE, DiezJ, et al.Immunohistochemical detection of chloride/bicarbonate anion exchangers in human liver. Hepatology1994;19:1400. CrossRef

182. BanalesJM, ArenasF, Rodriguez‐OrtigosaCM, et al.Bicarbonate‐rich choleresis induced by secretin in normal rat is taurocholate‐dependent and involves AE2 anion exchanger. Hepatology2006;43:266. CrossRef

183. MarinelliRA, PhamL, AgreP, et al.Secretin promotes osmotoc water transport in rat cholangiocytes by increasing aquaporin‐1 water channels in plasma membrane. Evidence for secretin‐induced vesicular translocation of aquaporin‐1. J Biol Chem1997;272:12984. CrossRef

184. MarinelliRA, PhamLD, TietzPS, et al.Expression of aquaporin‐4 water channels in rat cholangiocytes. Hepatology2000;31:1313. CrossRef

185. TietzPS, McNivenMA, SplinterPL, et al.Cytoskeletal and motor proteins facilitate trafficking of AQP1‐containing vesicles in cholangiocytes. Biol Cell2006;98:43. CrossRef

186. SplinterPL, MasyukAI, MarinelliRA, et al.AQP4 transfected into mouse cholangiocytes promotes water transport in biliary epithelia. Hepatology2004;39:109. CrossRef

187. DuttaAK, KhimjiAK, SatheM, et al.Identification and functional characterization of the intermediate conductance Ca2+‐activated K+ channel (IK‐1) in biliary epithelium. Am J Physiol Gastrointest Liver Physiol2009;297:G1009. CrossRef

188. FeranchakAP, DoctorRB, TroetschM, et al.Calcium‐dependent regulation of secretion in biliary epithelial cells: the role of apamin‐sensitive SK channels. Gastroenterology2004;127:903. CrossRef

189. HuflejtME, BlumRA, MillerSG, et al.Regulated Cl transport, K and Cl permeability and exocytosis in T84 cells. J Clin Invest1994;93:1900. CrossRef

190. CliffWH, FrizzellRA. Separate chloride conductances activated by cAMP and Ca2+ in Cl‐ secreting epithelial cells. Proc Natl Acad Sci U S A1990;87:4956. CrossRef

191. SchlenkerT, FitzJG. Calcium‐activated chloride channels in a human biliary cell line: regulation by calcium/calmodulin‐dependent protein kinase. Am J Physiol1996;271:G304.

192. RomanRM, BodilyK, WangY, et al.Activation of protein kinase C alpha couples cell volume to membrane Cl‐ permeability in HTC hepatoma and Mz‐ChA‐1 cholangiocarcinoma cells. Hepatology1998;28:1073. CrossRef

193. FeranchakAP, RomanRM, DoctorRB, et al.The lipid products of phosphoinositide 3‐kinase contribute to regulation of cholangiocyte ATP and chloride transport. J Biol Chem1999;274:30979. CrossRef

194. McGillJ, GettysTW, BasavappaS, et al.GTP‐binding proteins regulate high conductance anion channels in rat bile duct epithelial cells. J Membr Biol1993;133:253. CrossRef

195. CohnJA, StrongTA, PicciottoMA, et al.Localization of CFTR in human bile duct epithelial cells. Gastroenterology1993;105:1857.

196. DuttaAK, KhimjiAK, KresgeC, et al.Identification and functional characterization of TMEM16A, a Ca2+‐activated Cl‐ channel activated by extracellular nucleotides, in biliary epithelium. J Biol Chem2011;286:766. CrossRef

197. DuttaAK, WooK, KhimjiAK, et al.Mechanosensitive Cl‐ secretion in biliary epithelium mediated through TMEM16A. Am J Physiol Gastrointest Liver Physiol2013;304:G87. CrossRef

198. FitzJG, CohnJA. Regulation of CFTR and other chloride channels in biliary epithelial cells. In: SiricaA, LongneckerD(eds). Biliary and Pancreatic Ductal Epithelia: Pathobiology and Pathophysiology. Philadelphia: Marcel Dekker; 1996: 107.

199. LevineRA, HallRC. Cyclic AMP in secretin choleresis. Evidence for a regulatory role in man and baboons but not in dogs. Gastroenterology1976;70:537.

200. StrazzaboscoM, MennoneA, BoyerJL. Intracellular pH regulation in isolated rat bile duct epithelial cells. J Clin Invest1991;87:1503. CrossRef

201. GlaserSS, GaudioE, RaoA, et al.Morphological and functional heterogeneity of the mouse intrahepatic biliary epithelium. Lab Invest2009;89:456. CrossRef

202. UenoY, AlpiniG, YahagiK, et al.Evaluation of differential gene expression by microarray analysis in small and large cholangiocytes isolated from normal mice. Liver Int2003;23:449. CrossRef

203. ColomboC, ApostoloMG, FerrariM, et al.Analysis of risk factors for the development of liver disease associated with cystic fibrosis. J Pediatr1994;124:393. CrossRef

204. ColomboC, BattezzatiPM, CrosignaniA, et al.Liver disease in cystic fibrosis: a prospective study on incidence, risk factors, and outcome. Hepatology2002;36:1374. CrossRef

205. FeranchakAP, SokolRJ. Cholangiocyte biology and cystic fibrosis liver disease. Semin Liver Dis2001;21:471. CrossRef

206. SatheM, FeranchakAP. Liver disease. In: AllenJL, PanitchHN, RubensteinRC(eds). Cystic Fibrosis: Lung Biology in Health and Disease. New York: Informa Health Care; 2010: 285.

207. ClarkeLL, GrubbBR, YankaskasJ, et al.Relationship of a non‐cystic fibrosis transmembrane conductance regulator‐mediated chloride conductance to organ‐level disease in cftr(‐/‐) mice. Proc Natl Acad Sci U S A1994;91:479. CrossRef

208. MinagawaN, NagataJ, ShibaoK, et al.Cyclic AMP regulates bicarbonate secretion in cholangiocytes through release of ATP into bile. Gastroenterology2007;133:1592. CrossRef

209. FiorottoR, SpirliC, FabrisL, et al.Ursodeoxycholic acid stimulates cholangiocyte fluid secretion in mice via CFTR‐dependent ATP secretion. Gastroenterology2007;133:1603. CrossRef

210. GrafJ, GautamA, BoyerJL. Isolated rat hepatocyte couplets: a primary secretory unit for electrophysiologic studies of bile secretory function. Proc Natl Acad Sci U S A1984;81:6516. CrossRef

211. GrafJ, PetersenOH. Cell membrane potential and resistance in liver. J Physiol1978;284:105. CrossRef

212. WondergemR, HarderDR. Membrane potential measurements during rat liver regeneration. J Cell Physiol1980;102:193. CrossRef

213. MukhopadhyayS, AnanthanarayananM, StiegerB, et al.Sodium taurocholate cotransporting polypeptide is a serine, threonine phosphoprotein and is dephosphorylated by cyclic adenosine monophosphate. Hepatology1998;28:1629. CrossRef

214. MukhopadhyayS, WebsterCR, AnwerMS. Role of protein phosphatases in cyclic AMP‐mediated stimulation of hepatic Na+/taurocholate cotransport. J Biol Chem1998;273:30039. CrossRef

215. KippH, AriasIM. Intracellular trafficking and regulation of canalicular ATP‐binding cassette transporters. Semin Liver Dis2000;20:339. CrossRef

216. BoyerJL, SorokaCJ. Vesicle targeting to the apical domain regulates bile excretory function in isolated rat hepatocyte couplets. Gastroenterology1995;109:1600. CrossRef

217. BoyerJL. Nuclear receptor ligands: rational and effective therapy for chronic cholestatic liver disease?Gastroenterology2005;129:735. CrossRef

218. KarpenSJ. Nuclear receptor regulation of hepatic function. J Hepatol2002;36:832. CrossRef

219. ParksDJ, BlanchardSG, BledsoeRK, et al.Bile acids: natural ligands for an orphan nuclear receptor. Science1999;284:1365. CrossRef

220. HalilbasicE, ClaudelT, TraunerM. Bile acid transporters and regulatory nuclear receptors in the liver and beyond. J Hepatol2013;58:155. CrossRef

221. ClaudelT, ZollnerG, WagnerM, et al.Role of nuclear receptors for bile acid metabolism, bile secretion, cholestasis, and gallstone disease. Biochim Biophys Acta2011;1812:867. CrossRef

222. MakishimaM, OkamotoAY, RepaJJ, et al.Identification of a nuclear receptor for bile acids. Science1999;284:1362. CrossRef

223. WangH, ChenJ, HollisterK, et al.Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell1999;3:543. CrossRef

224. TuH, OkamotoAY, ShanB. FXR, a bile acid receptor and biological sensor. Trends Cardiovasc Med2000;10:30. CrossRef

225. DensonLA, SturmE, EchevarriaW, et al.The orphan nuclear receptor, shp, mediates bile acid‐induced inhibition of the rat bile acid transporter, ntcp. Gastroenterology2001;121:140. CrossRef

226. KarpenSJ, SunAQ, KudishB, et al.Multiple factors regulate the rat liver basolateral sodium‐dependent bile acid cotransporter gene promoter. J Biol Chem1996;271:15211. CrossRef

227. FiorucciS, ZampellaA, DistruttiE. Development of FXR, PXR and CAR agonists and antagonists for treatment of liver disorders. Curr Top Med Chem2012;12:605. CrossRef

228. ZunigaS, FirrincieliD, HoussetC, et al.Vitamin D and the vitamin D receptor in liver pathophysiology. Clin Res Hepatol Gastroenterol2011;35:295. CrossRef

229. CalkinAC, TontonozP. Transcriptional integration of metabolism by the nuclear sterol‐activated receptors LXR and FXR. Nat Rev Mol Cell Biol2012;13:213.

230. ChianaleJ, VollrathV, WielandtAM, et al.Fibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse. Biochem J1996;314:781. CrossRef

231. KatoA, GoresG, LaRussoN. Secretin stimulates exocytosis in isolated bile duct epithelial cells by a cAMP‐mediated mechanism. J Biol Chem1992;267:15523.

232. RobertsSK, YanoM, UenoY, et al.Cholangiocytes express the aquaporin CHIP and transport water via a channel‐mediated mechanism. Proc Natl Acad Sci U S A1994;91:13009. CrossRef

233. TietzPS, AlpiniG, PhamL, et al.Somatostatin inhibits secretin‐induced ductal hypercholeresis and exocytosis by cholangiocytes. Am J Physiol1995;269:G110.

234. GlaserSS, RodgersRE, PhinizyJL, et al.Gastrin inhibits secretin‐induced ductal secretion by interaction with specific receptors on rat cholangiocytes. Am J Physiol1997;273:G1061.

235. CaligiuriA, GlaserS, RodgersRE, et al.Endothelin‐1 inhibits secretin‐stimulated ductal secretion by interacting with ETA receptors on large cholangiocytes. Am J Physiol1998;275:G835.

236. ChoWK, MennoneA, RydbergSA, et al.Bombesin stimulates bicarbonate secretion from rat cholangiocytes: implications for neural regulation of bile secretion. Gastroenterology1997;113:311. CrossRef

237. ChoWK, BoyerJL. Vasoactive intestinal popypeptide is a potent regulator of bile secretion from rat cholangiocytes. Gastroenterology1999;117:420. CrossRef

238. AlvaroD, JezequelAM, BassottiC, et al.Role and mechanisms of action of acetylcholine in the regulation of rat cholangiocyte secretory functions. J Clin Invest1999;100:1349. CrossRef

239. DranoffJA, MasyukAI, KruglovEA, et al.Polarized expression and function of P2Y ATP receptors in rat bile duct epithelia. Am J Physiol Gastrointest Liver Physiol2001;281:G1059.

240. DoctorRB, MatzakosT, McWilliamsR, et al.Purinergic regulation of cholangiocyte secretion: identification of a novel role for P2X receptors. Am J Physiol Gastrointest Liver Physiol2005;288:G779. CrossRef

241. AlpiniG, GlaserS, RobertsonW, et al.Bile acids stimulate proliferative and secretory events in large but not small cholangiocytes. Am J Physiol1997;273:G518.

242. LazaridisKN, PhamL, TietzPS, et al.Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium‐dependent bile acid transporter. J Clin Invest1997;100:2714. CrossRef

243. KeitelV, HaussingerD. TGR5 in the biliary tree. Dig Dis2011;29:45. CrossRef

244. MasyukAI, HuangBQ, RadtkeBN, et al.Ciliary subcellular localization of TGR5 determines the cholangiocyte functional response to bile acid signaling. Am J Physiol Gastrointest Liver Physiol2013;304:G1013. CrossRef

245. KeitelV, UllmerC, HaussingerD. The membrane‐bound bile acid receptor TGR5 (Gpbar‐1) is localized in the primary cilium of cholangiocytes. Biol Chem2010;391:785. CrossRef

246. FeranchakAP, RomanRM, SchwiebertEM, et al.Phosphatidyl inositol 3‐kinase represents a novel signal regulating cell volume through effects on ATP release. J Biol Chem1998;273:14906. CrossRef

247. ChariRS, SchutzSM, HaebigJA, et al.Adenosine nucleotides in bile. Am J Physiol1996;270:G246.

248. BraunsteinGM, RomanRM, ClancyJP, et al.Cystic fibrosis transmembrane conductance regulator facilitates ATP release by stimulating a separate ATP release channel for autocrine control of cell volume regulation. J Biol Chem2001;276:6621. CrossRef

249. RomanRM, LomriN, BraunsteinG, et al.Evidence for multidrug resistance‐1 P‐glycoprotein‐dependent regulation of cellular ATP permeability. J Membr Biol2001;183:165. CrossRef

250. GatofD, KilicG, FitzJG. Vesicular exocytosis contributes to volume‐sensitive ATP release in biliary cells. Am J Physiol Gastrointest Liver Physiol2004;286:G538. CrossRef

251. FeranchakAP, LewisMA, KresgeC, et al.Initiation of purinergic signaling by exocytosis of ATP‐containing vesicles in liver epithelium. J Biol Chem2010;285:8138. CrossRef

252. SatheMN, WooK, KresgeC, et al.Regulation of purinergic signaling in biliary epithelial cells by exocytosis of SLC17A9‐dependent ATP‐enriched vesicles. J Biol Chem2011;286:25363. CrossRef

253. MasyukAI, HuangBQ, WardCJ, et al.Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia. Am J Physiol Gastrointest Liver Physiol2010;299:G990. CrossRef

254. LeeY, ElAS, WoodMJ. Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet2012;21:R125. CrossRef

255. SunD, ZhuangX, ZhangS, et al.Exosomes are endogenous nanoparticles that can deliver biological information between cells. Adv Drug Deliv Rev2013;65:342. CrossRef

256. MasyukAI, MasyukTV, LaRussoNF. Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases. J Hepatol2013;59:621. CrossRef

257. WooK, DuttaAK, PatelV, et al.Fluid flow induces mechanosensitive ATP release, calcium signalling and Cl‐ transport in biliary epithelial cells through a PKCzeta‐dependent pathway. J Physiol2008;586:2779. CrossRef

258. ScharschmidtBF, LakeJR. Hepatocellular bile acid transport and ursodeoxycholic acid hypercholeresis. Dig Dis Sci1989;34(12 Suppl):5S. CrossRef

259. MasyukAI, GradiloneSA, BanalesJM, et al.Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors. Am J Physiol Gastrointest Liver Physiol2008;295:G725. CrossRef

260. MasyukAI, MasyukTV, LaRussoNF. Cholangiocyte primary cilia in liver health and disease. Dev Dyn2008;237:2007. CrossRef

261. GradiloneSA, MasyukAI, SplinterPL, et al.Cholangiocyte cilia express TRPV4 and detect changes in luminal tonicity inducing bicarbonate secretion. Proc Natl Acad Sci U S A2007;104:19138. CrossRef

262. MasyukTV, HuangBQ, WardCJ, et al.Defects in cholangiocyte fibrocystin expression and ciliary structure in the PCK rat. Gastroenterology2003;125:1303. CrossRef

263. TorriceA, CardinaleV, GattoM, et al.Polycystins play a key role in the modulation of cholangiocyte proliferation. Dig Liver Dis2010;42:377. CrossRef

264. JaeschkeH, GoresGJ, CederbaumAI, et al.Mechanisms of hepatotoxicity. Toxicol Sci2002;65:166. CrossRef

265. YerushalmiB, DahlR, DevereauxMW, et al.Bile acid‐induced rat hepatocyte apoptosis is inhibited by antioxidants and blockers of the mitochondrial permeability transition. Hepatology2001;33:616. CrossRef

266. SokolRJ, DevereauxM, DahlR, et al.Let there be bile"–understanding hepatic injury in cholestasis. J Pediatr Gastroenterol Nutr2006;43(Suppl 1):S4. CrossRef

267. HiguchiH, GoresGJ. Mechanisms of liver injury: an overview. Curr Mol Med2003;3:483. CrossRef

268. GartungC, AnanthanarayananM, RahmanMA, et al.Down‐regulation of expression and function of the rat liver Na+/bile acid cotransporter in extrahepatic cholestasis. Gastroenterology1996;110:199. CrossRef

269. BohanA, ChenWS, DensonLA, et al.Tumor necrosis factor alpha‐dependent up‐regulation of Lrh‐1 and Mrp3(Abcc3) reduces liver injury in obstructive cholestasis. J Biol Chem2003;278:36688. CrossRef

270. ClaytonRJ, IberFL, RuebnerBH, et al.Byler disease. Fatal familial intrahepatic cholestasis in an Amish kindred. Am J Dis Child1969;117:112. CrossRef

271. AlonsoEM, SnoverDC, MontagA, et al.Histologic pathology of the liver in progressive familial intrahepatic cholestasis. J Pediatr Gastroenterol Nutr1994;18:128. CrossRef

272. KniselyAS. Progressive familial intrahepatic cholestasis: a personal perspective. Pediatr Dev Pathol2000;3:113. CrossRef

273. KlompLW, VargasJC, van MilSW, et al.Characterization of mutations in ATP8B1 associated with hereditary cholestasis. Hepatology2004;40:27. CrossRef

274. BullLN, CarltonVE, StrickerNL, et al.Genetic and morphological findings in progressive familial intrahepatic cholestasis (Byler disease [PFIC‐1] and Byler syndrome): evidence for heterogeneity. Hepatology1997;26:155. CrossRef

275. van MilSW, KlompLW, BullLN, et al.FIC1 disease: a spectrum of intrahepatic cholestatic disorders. Semin Liver Dis2001;21:535. CrossRef

276. van MilSW, van OortMM, van der BergIE, et al.Fic1 is expressed at apical membranes of different epithelial cells in the digestive tract and is induced in the small intestine during postnatal development of mice. Pediatr Res2004;56:981. CrossRef

277. LykavierisP, van MilS, CresteilD, et al.Progressive familial intrahepatic cholestasis type 1 and extrahepatic features: no catch‐up of stature growth, exacerbation of diarrhea, and appearance of liver steatosis after liver transplantation. J Hepatol2003;39:447. CrossRef

278. EgawaH, YorifujiT, SumazakiR, et al.Intractable diarrhea after liver transplantation for Byler's disease: successful treatment with bile adsorptive resin. Liver Transpl2002;8:714. CrossRef

279. WhitingtonPF, WhitingtonGL. Partial external diversion of bile for the treatment of intractable pruritus associated with intrahepatic cholestasis. Gastroenterology1988;95:130.

280. KurbegovAC, SetchellKD, HaasJE, et al.Biliary diversion for progressive familial intrahepatic cholestasis: improved liver morphology and bile acid profile. Gastroenterology2003;125:1227. CrossRef

281. MelterM, RodeckB, KardorffR, et al.Progressive familial intrahepatic cholestasis: partial biliary diversion normalizes serum lipids and improves growth in noncirrhotic patients. Am J Gastroenterol2000;95:3522. CrossRef

282. BullLN, van EijkMJ, PawlikowskaL, et al.A gene encoding a P‐type ATPase mutated in two forms of hereditary cholestasis. Nat Genet1998;18:219. CrossRef

283. BalsellsF, WyllieR, SteffenR, et al.Benign recurrent intrahepatic cholestasis: improvement of pruritus and shortening of the symptomatic phase with rifampin therapy: a case report. Clin Pediatr (Phila)1997;36:483. CrossRef

284. KeitelV, BurdelskiM, VojnisekZ, et al.De novo bile salt transporter antibodies as a possible cause of recurrent graft failure after liver transplantation: a novel mechanism of cholestasis. Hepatology2009;50:510. CrossRef

285. JaraP, HierroL, Martinez‐FernandezP, et al.Recurrence of bile salt export pump deficiency after liver transplantation. N Engl J Med2009;361:1359. CrossRef

286. van MilSW, van der WoerdWL, van der BruggeG, et al.Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11. Gastroenterology2004;127:379. CrossRef

287. JacqueminE, de VreeJM, CresteilD, et al.The wide spectrum of multidrug resistance 3 deficiency: from neonatal cholestasis to cirrhosis of adulthood. Gastroenterology2001;120:1448. CrossRef

288. DeleuzeJF, JacqueminE, DubuissonC, et al.Defect of multidrug‐resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis. Hepatology1996;23:904. CrossRef

289. Oude ElferinkRPJ, OttenhoffR, van WijlandM, et al.Regulation of biliary lipid secretion by mdr2 P‐glycoprotein in the mouse. J Clin Invest1995;95:31. CrossRef

290. de VreeJM, JacqueminE, SturmE, et al.Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc Natl Acad Sci U S A1998;95:282. CrossRef

291. BoveKE, HeubiJE, BalistreriWF, et al.Bile acid synthetic defects and liver disease: a comprehensive review. Pediatr Dev Pathol2004;7:315.

292. SetchellKD, O'ConnellNC. Disorders of bile acid synthesis and metabolism: a metabolic basis for liver disease. In: SuchyFJ, SokolRJ, BalistreriWF(eds). Liver Disease in Children, 3rd edn. Cambridge: Cambridge University Press; 2007: 736. CrossRef

293. FeranchakAP. Hepatobiliary complications of cystic fibrosis. Curr Gastroenterol Rep2004;6:231. CrossRef

294. SokolRJ, DuriePR. Recommendations for management of liver and biliary tract disease in cystic fibrosis. Cystic Fibrosis Foundation Hepatobiliary Disease Consensus Group. J Pediatr Gastroenterol Nutr1999;28 (Suppl 1):S1. CrossRef

295. LindbladA, GlaumannH, StrandvikB. Natural history of liver disease in cystic fibrosis. Hepatology1999;30:1151. CrossRef

296. AlagilleD, OdievreM, GautierM, et al.Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr1975;86:63. CrossRef

297. KamathBM, SpinnerNB, PiccoliDA. Alagille syndrome. In: SuchyFJ, SokolRJ, BalistreriWF(eds). Liver Disease in Children, 3rd edn. Cambridge: Cambridge University Press; 2007: 326. CrossRef

298. EmerickKM, RandEB, GoldmuntzE, et al.Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology1999;29:822. CrossRef

299. OdaT, ElkahlounAG, PikeBL, et al.Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet1997;16:235. CrossRef

300. LiL, KrantzID, DengY, et al.Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet1997;16:243. CrossRef

301. McDaniellR, WarthenDM, Sanchez‐LaraPA, et al.NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet2006;79:169. CrossRef

302. ZongY, PanikkarA, XuJ, et al.Notch signaling controls liver development by regulating biliary differentiation. Development2009;136:1727. CrossRef

303. HoffenbergEJ, NarkewiczMR, SondheimerJM, et al.Outcome of syndromic paucity of interlobular bile ducts (Alagille syndrome) with onset of cholestasis in infancy. J Pediatr1995;127:220. CrossRef

304. SokolRJ, MackC, NarkewiczMR, et al.Pathogenesis and outcome of biliary atresia: current concepts. J Pediatr Gastroenterol Nutr2003;37:4. CrossRef

305. BezerraJA. Potential etiologies of biliary atresia. Pediatr Transplant2005;9:646. CrossRef

306. MazziottiMV, WillisLK, HeuckerothRO, et al.Anomalous development of the hepatobiliary system in the Inv mouse. Hepatology1999;30:372. CrossRef

307. MackCL, FeldmanAG, SokolRJ. Clues to the etiology of bile duct injury in biliary atresia. Semin Liver Dis2012;32:307. CrossRef

308. MackCL. The pathogenesis of biliary atresia: evidence for a virus‐induced autoimmune disease. Semin Liver Dis2007;27:233. CrossRef

309. ShivakumarP, SablaG, MohantyS, et al.Effector role of neonatal hepatic CD8+ lymphocytes in epithelial injury and autoimmunity in experimental biliary atresia. Gastroenterology2007;133:268. CrossRef

310. MackCL, FaltaMT, SullivanAK, et al.Oligoclonal expansions of CD4+ and CD8+ T‐cells in the target organ of patients with biliary atresia. Gastroenterology2007;133:278. CrossRef