The Hyperosmolarity-induced and Fyn-mediated retrieval of Mrp2, Bsep- and Ntcp is sensitive to cyclic AMP and TUDC

Introduction: In perfused rat liver, hyperosmolarity induces Fyn-mediated Mrp2-/Bsep-retrieval from the canalicular membrane (Cantore et al., JBC 2011) leading to cholestasis. Cyclic AMP and TUDC induce choleresis by the increase of Na+-taurocholate cotransport via Ntcp-insertion to hepatocyte basolateral plasma membranes. The aim of the study was to elucidate the underlying signaling events. Methods: Rat livers were perfused with either normo- (305 mosmol/L) or hyperosmotic medium (385 mosmol/L). Liver tissue was processed for immunohistochemical Mrp2-, Bsep- and Ntcp-staining following automatic analysis of tr…