Interaction between ethanol metabolism and mixed-function oxidation in alcohol dehydrogenase positive and negative deermice.
To assess the effect of non alcohol dehydrogenase (ADH) ethanol metabolism on mixed-function oxidation, aminopyrine demethylation was studied in vivo and in vitro in deermice having normal liver ADH (ADH+) or lacking it (ADH-), in the presence and absence of ethanol. When injected 15 min prior to administration of [14C]aminopyrine, ethanol reduced the 14CO2 exhalation rate in both ADH- and ADH+ deermice. The inhibitory effect of ethanol was dose dependent in both strains, and there was no significant difference between strains. Chronic ethanol feeding increased 14CO2 production from [14C]aminopyrine in both animal strains (ADH- alcohol 5.9 +/- 1.3 vs ADH- control 2.9 +/- 0.03, P less than 0.025; ADH+ alcohol 5.9 +/- 0.3 vs ADH+ control 2.7 +/- 1.3 nmoles aminopyrine/100 g body wt/min, P less than 0.001). Alcohol feeding also induced aminopyrine N-demethylase activity measured in vitro. This induction was more pronounced in ADH- deermice. Ethanol also inhibited aminopyrine demethylation in liver homogenates from ADH- and ADH+ animals in a dose-dependent manner and to a comparable degree in both strains. The kinetics of aminopyrine N-demethylase inhibition by ethanol was competitive in the microsomal fraction from ADH- as well as ADH+ animals. These results suggest that inhibition of mixed-function oxidation by ethanol may be due to an effect of ethanol on the hepatic microsomes rather than to redox changes produced by ADH-mediated ethanol oxidation. Further, chronic ethanol feeding increased microsomal aminopyrine demethylation independently of the presence of ADH.
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000032:analysis*; D000632:Aminopyrine / Q000378:metabolism; D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors*; D000818:Animals; D002250:Carbon Radioisotopes; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010542:Peromyscus
D002250:Carbon Radioisotopes; D000632:Aminopyrine; D000431:Ethanol; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D000633:Aminopyrine N-Demethylase