Functional expression of the apical Na+-dependent bile acid transporter in large but not small rat cholangiocytes

Abstract

Background and Aims: Bile acids interact with cholangiocytes, resulting in cholangiocyte proliferation and increases in ductal bile secretion in large but not small cholangiocytes. It was proposed that for bile acids to exert these effects on cholangiocytes, a specific uptake mechanism must be present in cholangiocytes. The aim of this study was to show the expression of a bile acid transporter in cholangiocytes. Methods: Small and large cholangiocytes or intrahepatic bile duct units (IBDUs) were isolated from normal rats, and gene expression for the apical Na+-dependent bile acid transporter (ABAT) and the 14-kilodalton ileal cytosolic binding protein (IBABP) was assessed by ribonuclease-protection assays. Tissue and subcellular distribution of bile acid transporters was also studied. [14C]- Taurocholate uptake into cholangiocytes was determined. Results: Both ABAT and IBABP messenger RNAs were detected in large but not small cholangiocytes. By immunohistochemistry, ABAT was present in large but not small cholangiocytes. Immunofluorescence showed ABAT to be present in the apical membrane of large IBBUs. A Na+-dependent saturable uptake of taurocholate was present in large but not small cholangiocytes. Conclusions: These proteins may mediate bile acid uptake from the duct lumen in large ducts, resulting in modification of canalicular bile secretion and modulation of ductal bile secretion and growth.