Impairment of glucagon-induced hepatic system a activity by short-term ethanol administration in the rat

Abstract

Background/Aims: System A is a membrane-bound, hormonally regulated carrier of amino acids that is induced by liver regeneration and impaired by ethanol. The mechanism of ethanol inhibition of system A is unknown; this study examines the effects of ethanol on the subcellular expression of system A activity following hormonal induction. Methods: Following hormonal treatment and short-term ethanol administration to rats, isolated liver Golgi and plasma membrane vesicles were examined for system A transport, and the kinetic parameters were determined. Results: Four hours after ethanol administration, the initial rate of system A activity was depressed 30% ± 9% and 19% ± 7% into Golgi and plasma membrane vesicles, respectively. The affinity constant of 2-(methylamino)-isobutyric acid uptake was unchanged between control and ethanol-treated vesicles, regardless of their subcellular origin. However, the maximal velocity of system A transport decreased from 1030 to 850 pmol ·mg−1 protein ·10 s−1 in Golgi vesicles and from 740 to 355 pmol ·mg−1 protein 10 s−1 in plasma membrane vesicles. Conclusions: Ethanol impairs hormonally induced system A activity in Golgi as well as in the plasma membrane vesicles. Ethanol potentially reduces glucagon induction of system A activity through an impairment of carrier biosynthesis or expression.