DIFFERENCES AMONG THE ACTION OF PHENOBARBITAL, METHYLCHOLANTHRENE AND MALE SEX HORMONE ON MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEMS OF RAT LIVER

Abstract

The administration of phenobarbital, phenaglycodol, glutethimide, chlorcyclizine, chlorpromazine or other different kinds of drugs induce an increase in the activities of drug-metabolizing enzyme system of liver microsome (1-3). Moreover, the administration of caricnogenic polycyclic hydrocarbons, such as 20-methylcholanthrene or 3, 4-benzopyrene also induce an increase in the activities of drug-metabolizing enzyme systems of liver microsome (4, 5), however, the enzyme systems stimulated by methylcholanthrene or benzopyrene are apparently different from which stimulated by phenobarbital (4, 6, 7). On the other hand, Brodie et al. demonstrated that the liver microsomes from male rats metabolized hexobarbital more rapidly than the liver microsomes from female rats did and the castration of male rats abolished the sex difference and the administration of teststerone restored the sex difference. Moreover, Kato et al. demonstrated that synthetic anabolic hormone, such as 4-chlorteststerone increased activities of strychnine on carisoprodol metabolizing enzymes of liver microsomes of castrated male and female rats (8, 9). However, Kato et al. observed that the single injection of phenobarbital or methylcholanthrene increased the activities of the drug-metabolizing enzyme system of liver microsomes already within 24 hours after the administration, while single injection of teststerone did not increase the activities of the enzyme systems and the activities were increased after successive injection of 4-5 days (10). Furthermore, Kato and Gilllette observed that the sex difference in the metabolism of drugs by liver microsomal enzymes was not observed in all of the enzyme systems, and some enzyme systems had no clear sex difference (11). These results indicate that the action of phenobarbital, methylcholanthrene and male sex hormone on microsomal drug-metabolizing enzyme systems of rat liver is likely different. The purpose of present communication is to elucidate these differences.