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Physiol. Rev. 83: 633-671, 2003; doi:10.1152/physrev.00027.2002
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Physiological Reviews, Vol. 83, No. 2, April 2003, pp. 633-671; 10.1152/physrev.00027.2002.
Copyright ©2003 by the American Physiological Society

Bile Salt Transporters: Molecular Characterization, Function, and Regulation

Michael Trauner and James L. Boyer

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Karl-Franzens University, School of Medicine, Graz, Austria; and Department of Medicine and Liver Center, Yale University School of Medicine, New Haven, Connecticut

Trauner, Michael and James L. Boyer. Bile Salt Transporters: Molecular Characterization, Function, and Regulation. Physiol. Rev. 83: 633-671, 2003.Molecular medicine has led to rapid advances in the characterization of hepatobiliary transport systems that determine the uptake and excretion of bile salts and other biliary constituents in the liver and extrahepatic tissues. The bile salt pool undergoes an enterohepatic circulation that is regulated by distinct bile salt transport proteins, including the canalicular bile salt export pump BSEP (ABCB11), the ileal Na+-dependent bile salt transporter ISBT (SLC10A2), and the hepatic sinusoidal Na+- taurocholate cotransporting polypeptide NTCP (SLC10A1). Other bile salt transporters include the organic anion transporting polypeptides OATPs (SLC21A) and the multidrug resistance-associated proteins 2 and 3 MRP2,3 (ABCC2,3). Bile salt transporters are also present in cholangiocytes, the renal proximal tubule, and the placenta. Expression of these transport proteins is regulated by both transcriptional and posttranscriptional events, with the former involving nuclear hormone receptors where bile salts function as specific ligands. During bile secretory failure (cholestasis), bile salt transport proteins undergo adaptive responses that serve to protect the liver from bile salt retention and which facilitate extrahepatic routes of bile salt excretion. This review is a comprehensive summary of current knowledge of the molecular characterization, function, and regulation of bile salt transporters in normal physiology and in cholestatic liver disease and liver regeneration.




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R. Z. Turncliff, P. J. Meier, and K. L. R. Brouwer
EFFECT OF DEXAMETHASONE TREATMENT ON THE EXPRESSION AND FUNCTION OF TRANSPORT PROTEINS IN SANDWICH-CULTURED RAT HEPATOCYTES
Drug Metab. Dispos., August 1, 2004; 32(8): 834 - 839.
[Abstract] [Full Text] [PDF]

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 J. Lipid Res.Home page
W. Khovidhunkit, M.-S. Kim, R. A. Memon, J. K. Shigenaga, A. H. Moser, K. R. Feingold, and C. Grunfeld
Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host
J. Lipid Res., July 1, 2004; 45(7): 1169 - 1196.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
D. Jung, B. Hagenbuch, M. Fried, P. J. Meier, and G. A. Kullak-Ublick
Role of liver-enriched transcription factors and nuclear receptors in regulating the human, mouse, and rat NTCP gene
Am J Physiol Gastrointest Liver Physiol, May 1, 2004; 286(5): G752 - G761.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R. H. Ho, B. F. Leake, R. L. Roberts, W. Lee, and R. B. Kim
Ethnicity-dependent Polymorphism in Na+-taurocholate Cotransporting Polypeptide (SLC10A1) Reveals a Domain Critical for Bile Acid Substrate Recognition
J. Biol. Chem., February 20, 2004; 279(8): 7213 - 7222.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
Y. Inoue, A.-M. Yu, J. Inoue, and F. J. Gonzalez
Hepatocyte Nuclear Factor 4{alpha} Is a Central Regulator of Bile Acid Conjugation
J. Biol. Chem., January 23, 2004; 279(4): 2480 - 2489.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. Figge, F. Lammert, B. Paigen, A. Henkel, S. Matern, R. Korstanje, B. L. Shneider, F. Chen, E. Stoltenberg, K. Spatz, et al.
Hepatic Overexpression of Murine Abcb11 Increases Hepatobiliary Lipid Secretion and Reduces Hepatic Steatosis
J. Biol. Chem., January 23, 2004; 279(4): 2790 - 2799.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
D. Mesotten, G. Van den Berghe, C. Liddle, S. Coulter, F. McDougall, R. C. Baxter, and P. J. D. Delhanty
Growth Hormone Modulation of the Rat Hepatic Bile Transporter System in Endotoxin-Induced Cholestasis
Endocrinology, September 1, 2003; 144(9): 4008 - 4017.
[Abstract] [Full Text] [PDF]

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 Physiol. GenomicsHome page
M. A. Lyons, H. Wittenburg, R. Li, K. A. Walsh, M. R. Leonard, G. A. Churchill, M. C. Carey, and B. Paigen
New quantitative trait loci that contribute to cholesterol gallstone formation detected in an intercross of CAST/Ei and 129S1/SvImJ inbred mice
Physiol Genomics, August 15, 2003; 14(3): 225 - 239.
[Abstract] [Full Text] [PDF]


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