Impairment of glucagon-induced hepatic system A activity by short-term ethanol administration in the rat.
OBJECTIVE
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.
Mailliard
M E
ME
Department of Medicine, University of Florida, Gainesville.
Cariappa
R
R
Banks
R K
RK
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000096:biosynthesis*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D002352:Carrier Proteins; D000431:Ethanol; D005934:Glucagon