Secretin activation of the apical Na +-dependent bile acid transporter is associated with cholehepatic shunting in rats

Gianfranco Alpini, Shannon Glaser, Leonardo Baiocchi, Heather Francis, Xuefeng Xia, Gene LeSage

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

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 3H-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.

Original languageEnglish (US)
Pages (from-to)1037-1045
Number of pages9
JournalHepatology
Volume41
Issue number5
DOIs
StatePublished - May 2005

ASJC Scopus subject areas

  • Hepatology

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