Bile salt transporters: Molecular characterization, function, and regulation

被引:752
作者
Trauner, M
Boyer, JL
机构
[1] Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Ctr Liver, New Haven, CT 06520 USA
[3] Karl Franzens Univ Graz, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Graz, Austria
关键词
D O I
10.1152/physrev.00027.2002
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:633 / 671
页数:39
相关论文
共 399 条
[1]   Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1 [J].
Abe, T ;
Kakyo, M ;
Tokui, T ;
Nakagomi, R ;
Nishio, T ;
Nakai, D ;
Nomura, H ;
Unno, M ;
Suzuki, M ;
Naitoh, T ;
Matsuno, S ;
Yawo, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (24) :17159-17163
[2]   Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transports thyroid hormones and taurocholate and comparison with oatp2 [J].
Abe, T ;
Kakyo, M ;
Sakagami, H ;
Tokui, T ;
Nishio, T ;
Tanemoto, M ;
Nomura, H ;
Hebert, SC ;
Matsuno, S ;
Kondo, H ;
Yawo, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (35) :22395-22401
[3]   Identification of scavenger receptor SR-BI as a high density lipoprotein receptor [J].
Acton, S ;
Rigotti, A ;
Landschulz, KT ;
Xu, SZ ;
Hobbs, HH ;
Krieger, M .
SCIENCE, 1996, 271 (5248) :518-520
[4]   Intracellular transport of bile acids [J].
Agellon, LB ;
Torchia, EC .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, 1486 (01) :198-209
[5]   Transport activity of human MRP3 expressed in Sf9 cells: Comparative studies with rat MRP3 [J].
Akita, H ;
Suzuki, H ;
Hirohashi, T ;
Takikawa, H ;
Sugiyama, Y .
PHARMACEUTICAL RESEARCH, 2002, 19 (01) :34-41
[6]   Sinusoidal efflux of taurocholate is enhanced in Mrp2-deficient rat liver [J].
Akita, H ;
Suzuki, H ;
Sugiyama, Y .
PHARMACEUTICAL RESEARCH, 2001, 18 (08) :1119-1125
[7]   Functional expression of the apical Na+-dependent bile acid transporter in large but not small rat cholangiocytes [J].
Alpini, G ;
Glaser, SS ;
Rodgers, R ;
Phinizy, JL ;
Robertson, WE ;
Lasater, J ;
Caligiuri, A ;
Tretjak, Z ;
LeSage, GD .
GASTROENTEROLOGY, 1997, 113 (05) :1734-1740
[8]   Ursodeoxycholate and tauroursodeoxycholate inhibit cholangiocyte growth and secretion of BDL rats through activation of PKC alpha [J].
Alpini, G ;
Baiocchi, L ;
Glaser, S ;
Ueno, Y ;
Marzioni, M ;
Francis, H ;
Phinizy, JL ;
Angelico, M ;
LeSage, G .
HEPATOLOGY, 2002, 35 (05) :1041-1052
[9]   Bile acid feeding induces cholangiocyte proliferation and secretion: Evidence for bile acid-regulated ductal secretion [J].
Alpini, G ;
Glaser, SS ;
Ueno, Y ;
Rodgers, R ;
Phinizy, JL ;
Francis, H ;
Baiocchi, L ;
Holcomb, LA ;
Caligiuri, A ;
LeSage, GD .
GASTROENTEROLOGY, 1999, 116 (01) :179-186
[10]   Bile acid feeding increased proliferative activity and apical bile acid transporter expression in both small and large rat cholangiocytes [J].
Alpini, GP ;
Ueno, Y ;
Glaser, SS ;
Marzioni, M ;
Phinizy, JL ;
Francis, H ;
LaSage, G .
HEPATOLOGY, 2001, 34 (05) :868-876