Alterations of hepatic microsomal drug metabolism by glucagon

The effect of glucagon on the components of the hepatic microsomal electron transport chain (NADPH oxidase, NADPH cytochrome c reductase (EC 1.6.2.4), cytochrome P 450, and NADPH cytochrome P 450 reductase), and on two representative oxidative pathways (aminopyrine N demethylation, a type I substrate oxidation; and aniline p hydroxylation, a type II substrate oxidation) was determined. Microsomes from rats pretreated with glucagon (300 μg/kg per day for 3 days) showed a significant decrease in NADPH oxidase and aminopyrine N demethylation with a prolonged hexobarbital sleeping time, and a significant increase in aniline p hydroxylation. Microsomes from rats pretreated with a lower dose of glucagon (30 μg/kg per day for 3 days) showed a significant decrease in the microsomal N demethylation of aminopyrine. Glucagon had no effect when added in vitro to microsomes, suggesting that the in vivo effects of glucagon are mediated indirectly in the intact animal.