EFFECT OF PHENOBARBITAL ON THE LEVEL OF TRANSLATABLE RAT-LIVER EPOXIDE HYDROLASE MESSENGER-RNA

Liver poly(A)+RNA isolated from untreated and phenobarbital-treated rats was translated in the rabbit reticulocyte cell-free system to determine the level of translationally active epoxide hydrolase (EC 3.3.2.3) m[messenger]RNA. The in vitro translation systems were immunoprecipitated with rabbit IgG prepared against purified epoxide hydrolase and the amount of epoxide hydrolase synthesized by the lysate programmed with control and phenobarbital poly(A)+RNA was quantitated. The level of translatable epoxide hydrolase mRNA is increased 3-fold after chronic phenobarbital administration. This level of induction correlates well with the 5-fold induction in catalytic activity of epoxide hydrolase (using styrene 7,8-oxide as substrate) in microsomes isolated from phenobarbital-treated rats. Chronic phenobarbital administration increases the amount of functional epoxide hydrolase in rat liver microsomes by increasing the translatable mRNA level encoding for the enzyme. Whether the increase in mRNA is due to increased transcription or messenger stability is not known.