Prevention of estradiol 17β-d-glucuronide– induced canalicular transporter internalization by hormonal modulation of cAMP in rat hepatocytes
- Zucchetti, Andrés Ernesto
- Barosso, Ismael Ricardo
- Boaglio, Andrea Carolina
- Pellegrino, Jose Manuel
- Ochoa, Justina Elena
- Roma, Marcelo Gabriel
- Crocenzi, Fernando Ariel
- Sanchez Pozzi, Enrique Juan
DOIAbstract
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. Gluca...
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