Prevention of estradiol 17beta-D-glucuronide-induced canalicular transporter internalization by hormonal modulation of cAMP in rat hepatocytes.

ABSTRACT: In estradiol 17β-d-glucuronide (E17G)-induced cholestasis, the canalicular hepatocellular transporters bile salt export pump (Abcb11) and multidrug-resistance associated protein 2 (Abcc2) undergo endocytic internalization. cAMP stimulates the trafficking of transporter-containing vesicles to the apical membrane and is able to prevent internalization of these transporters in estrogen-induced cholestasis. Hepatocyte levels of cAMP are regulated by hormones such as glucagon and adrenaline (via the β2 receptor). We analyzed the effects of glucagon and salbutamol (a β2 adrenergic agonist) on function and localization of Abcb11 and Abcc2 in isolated rat hepatocyte couplets exposed to E17G and compared the mechanistic bases of their effects. Glucagon and salbutamol partially prevented the impairm

SUBMITTER: Zucchetti AE 

PROVIDER: S-EPMC3192868 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature