CONICET | Buscador de Institutos y Recursos Humanos

As reviewed by Marinelli et al. in a recent issue of Journal of Hepatology (1), there is increasing evidence suggesting that an impaired balance in the canalicular membrane insertion/retrieval of certain transporters leads to bile secretory dysfunction (i.e. cholestasis). Bile secretion is ultimately dependent upon the transport of osmotically active solutes across the apical membrane of the hepatocyte, e.g. mediated by the bile salt export pump (Bsep; Abcb11) and multidrug resistance-associated protein 2 (Mrp2; Abcc2), followed by the passive movement of water. The water channel protein aquaporin-8 (AQP8) seems to facilitate the osmotically induced canalicular membrane water transport and bile formation by hepatocytes (2). Bsep and Mrp2 undergo marked endocytic internalization from the canalicular membrane into intracellular vesicles after administration of the endogenous estrogen metabolite estradiol-17b-D-glucuronide (E217G) to rats, in parallel with decreased Bsep and Mrp2 transport activities (3, 4). Bile flow decreases in a dose-dependent manner shortly (15-20 min) after i.v. administration of a single dose of E217G (5).