Secretin activation of the apical Na+-dependent bile acid transporter is associated with cholehepatic shunting in rats.
The role of the cholangiocyte apical Na(+)-dependent bile acid transporter (ASBT) in bile formation is unknown. Bile acid absorption by bile ducts results in cholehepatic shunting, a pathway that amplifies the canalicular osmotic effects of bile acids. We tested in isolated cholangiocytes if secretin enhances ASBT translocation to the apical membrane from latent preexisting intracellular stores. In vivo, in bile duct-ligated rats, we tested if increased ASBT activity (induced by secretin pretreatment) results in cholehepatic shunting of bile acids. We determined the increment in taurocholate-dependent bile flow and biliary lipid secretion and taurocholate (TC) biliary transit time during high ASBT activity. Secretin stimulated colchicine-sensitive ASBT translocation to the cholangiocyte plasma membrane and (3)H-TC uptake in purified cholangiocytes. Consistent with increased ASBT promoting cholehepatic shunting, with secretin pretreatment, we found TC induced greater-than-expected biliary lipid secretion and bile flow and there was a prolongation of the TC biliary transit time. Colchicine ablated secretin pretreatment-dependent bile acid-induced choleresis, increased biliary lipid secretion, and the prolongation of the TC biliary transit. In conclusion, secretin stimulates cholehepatic shunting of conjugated bile acids and is associated with increased cholangiocyte apical membrane ASBT. Bile acid transport by cholangiocyte ASBT can contribute to hepatobiliary secretion in vivo.
Alpini
Gianfranco
G
Department of Internal Medicine, Scott & White Hospital and The Texas A&M University System Health Sciences Center, College of Medicine, Temple, TX, USA.
Glaser
Shannon
S
Baiocchi
Leonardo
L
Francis
Heather
H
Xia
Xuefeng
X
Lesage
Gene
G
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D001652:Bile Ducts / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity / Q000502:physiology; D002756:Cholagogues and Choleretics / Q000493:pharmacokinetics; D003078:Colchicine / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012633:Secretin / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D013656:Taurocholic Acid / Q000493:pharmacokinetics; D014316:Tritium
D001639:Bicarbonates; D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; D014316:Tritium; D012633:Secretin; C071908:sodium-bile acid cotransporter; D013656:Taurocholic Acid; D003078:Colchicine