Induction of liver microsomal drug metabolism and inhibition of microsomal ribonuclease activity by phenobarbital

Abstract

Microsomal ribonuclease (RNase) activity was determined after the administration of phenobarbital (100 mg/kg, ip) to rats. Eighty percent inhibition of RNase activity occurred 48 hr prior to maximal stimulation of p-chloro- N-methylaniline demethylation. Thereafter, RNase activity increased to control levels. Inhibition of RNase activity was also observed in a dose-dependent manner when phenobarbital (25 mg/kg or 50 mg/kg twice daily) was administered to intact, adrenalectomized or hypophysectomized rats. These results suggested that RNase inhibition occurred during stimulation of drug metabolism in the absence of the pituitary or adrenal glands. Recombination experiments involving addition of 105,000 g liver supernatant fractions to control microsomes resulted in inhibition of RNase activity of the latter fractions. The administration of 3-methylcholanthrene (40 mg/kg, ip for 2 days) did not produce significant ( p > 0.05) inhibition of microsomal RNase. The results of this study suggested that RNase inhibition did not require an intact pituitary-adrenal axis during induction of drug metabolism by phenobarbital. The inhibition of RNase was probably due to the presence of a cytoplasmic inhibitor.