Relation Between Drug-Metabolizing Activity and Phospholipids in Hepatic Microsomes. I. Effects of Phenobarbital, Carbon Tetrachloride, and Actinomycin D

Abstract

The treatment of rats with phenobarbital caused a significant increase in hepatic microsomal content of protein and phospholipid in parallel with the induction of drug-metabolizing enzymes. In contrast, carbon tetrachloride significantly reduced microsomal protein, phospholipid, and drug-metabolizing enzyme activity. The opposing actions of these compounds were manifested mainly in the phosphatidylethanolamine, phosphatidylcholine, and lysophosphatidylcholine fractions.Actinomycin D was found to block all the effects of phenobarbital except for the increase in lysophosphatidylcholine which was inhibited only by about 50%. Actinomycin D alone significantly decreased drug-metabolizing enzyme activity and microsomal phospholipid content.