Induction by phenobarbital of the mRNA for a specific variant of rat liver microsomal cytochrome P-450

Abstract

The treatment of rats for 4 days with phenobarbital causes an apparent 3-fold increase in the amount of total liver cytochrome P-450. By sodium dodecyl sulfate/polyacrylamide-gel electrophoresis, metyrapone binding and immunoprecipitation; this increase was apparently due to a much larger increase in a resticted number of specific cytochrome P-450 variants. A radioimmunoassay technique demonstrated that the major phenobarbital-inducible variant, of MW 52,000, is induced 24-fold by phenobarbital. Immunoprecipitation analysis of products of translation in vitro with an antibody specific to the 52,000-MW cytochrome P-450 showed that phenobarbital induces the mRNA in polyribosomes for this variant 20-fold. Evidence is presented for the action of phenobarbital at the transcriptional and translational levels.