[HTML][HTML] Taurolithocholic acid exerts cholestatic effects via phosphatidylinositol 3-kinase-dependent mechanisms in perfused rat livers and rat hepatocyte couplets

U Beuers, GU Denk, CJ Soroka, R Wimmer… - Journal of Biological …, 2003 - ASBMB
Taurolithocholic acid (TLCA) is a potent cholestatic agent. Our recent work suggested that
TLCA impairs hepatobiliary exocytosis, insertion of transport proteins into apical hepatocyte
membranes, and bile flow by protein kinase Cε (PKCε)-dependent mechanisms. Products of
phosphatidylinositol 3-kinases (PI3K) stimulate PKCε. We studied the role of PI3K for TLCA-
induced cholestasis in isolated perfused rat liver (IPRL) and isolated rat hepatocyte couplets
(IRHC). In IPRL, TLCA (10 μmol/liter) impaired bile flow by 51%, biliary secretion of …