Role of RNA in induction of hepatic microsomal mixed function oxidases.

Induction of hepatic microsomal cytochrome P-450 and ethylmorphine N-demethylase activity by phenobarbital requires de novo synthesis of mRNA. Inhibition of RNA synthesis by alpha-amanitin given up to 8 hr after phenobarbital administration substantially inhibits this induction. However, beyond 8 hr after phenobarbital administration, RNA synthesis is not required for induction of these hepatic microsomal systems. Thus, mRNAs for cytochrome P-450 and ethylmorphine N-demethylase appear to be stable. Furthermore, these experiments reveal that the lag period for RNA synthesis approximates the length of the lag period for induction of the hepatic microsomal enzyme systems.