Title: Effect of Glucagon on Alcohol Dehydrogenase Activity in Rat Hepatocyte Culture
Abstract: The effect of glucagon on the activity of qlcohol dehydrogenase in rat hepatocyte culture was determined.Glucagon concentrations of 0.1 nM enhanced, whereas concentrations > 1 nM decreased, alcohol dehydrogenase.These effects became apparent after exposure of the cultures to glucagon for 4 or more days.The presence of corticosterone (1 p"MJ prev~nted thfl enhancing effect of 0.1 nM glucagon on alcohol dehydrogenase activity.The changes in alcohol dehydrogenase caused by glucagon were associated with parallel changes in the rate of ethanol elimination.Alcohol dehydrog~nase appears to be rate-limiting for ethanol oxidation, as uncoupling of oxidative phosphorylation did not modify the rate of ethanol elimination.These studies suggest a physiologic role of glucagon in enhancing liver alcohol dehydrogenase activity, whereas higher pharmacologic concentrations of glucagon have an opposite, depressant effect.Hepatic alcohol dehydrogenase is the principal enzyme responsible for ethanol oxidation.In the rat, hepatic alcohol dehydrogenase is altered by a variety of hormones.Alcohol dehydrogenase activity increases in experimentally induced uremia (1), and after stress (2), hypophysectomy (3), thyroidectomy (4), and castration (5,6).Glucagon, which markedly increases in uremia (7), after stress (8), and in catabolic states (9), has been reported to have variable effects on alcohol dehydrogenase and ethanol metabolism.Glucagon administration increased the rate of ethanol elimination in dogs (10) and the oxidation of ethanol by rat liver slices (11), and increased ethanol