The function of alkaline phosphatase in the liver: Regulation of intrahepatic biliary epithelium secretory activities in the rat

We studied the effects of alkaline phosphatase (AP) on the secretory proces ses of the rat intrahepatic biliary epithelium as well as the role of the i ntrahepatic biliary epithelium in the uptake and biliary secretion of exoge nous AP. The effects of acute and chronic administration of AP on bile secr etory parameters were investigated in vivo in normal and bile duct ligated (BDL) rats and in vitro in isolated rat bile duct units (IBDU), In vivo, ac ute AP administration decreased bile now and biliary bicarbonate excretion and abolished secretin choleresis in BDL rats but not in normal rats. On th e contrary, the AP inhibitor, levamisole, increased in BDL rat bile flow an d biliary bicarbonate excretion. In vitro, basal and secretin-stimulated Cl -/HCO3- exchanger activity in IBDU was immediately inhibited by AP intralum inal microinjection (apical exposure) but only after a prolonged exposure t o the basolateral pole. Levamisole increased the Cl-/HCO3- exchanger activi ty of IBDU, A significant basolateral uptake of AP occurs in IBDU with a pr ogressive transport to the apical domain. AP chronic treatment increased AP and gamma-glutamyltranspeptidase (gamma-GT) activities in the intrahepatic bile ducts and hepatocyte canalicular pole, promoted enlargement of bile c analiculi, and decreased bile flow and biliary bicarbonate excretion. In co nclusion, the intrahepatic biliary epithelium plays a role in the uptake an d biliary secretion of serum AP. AP inhibits the secretory processes of the intrahepatic biliary epithelium and induces features of intrahepatic chole stasis after chronic administration. These findings indicate that AP plays an active role in down-regulating the secretory activities of the intrahepa tic biliary epithelium.