Induction of hepatic cytochrome P-450 by phenobarbital in semi-aquatic frog (Rana pipiens).

Abstract

Hepatic microsomal cytochrome P450 (equivalent to rat P4502B1 isozymic form, a CYPIIB gene product) can be induced by pentobarbital (PB) in the adults of the semiaquatic frog, Rana pipiens (as in other terrestrial vertebrates), but not in adults of the aquatic frog Xenopus laevis or in bluegill sunfish (Lepomis macrochirus). The activity of PB-induced P450 (2B1) towards aldrin and pentoxyresorufin increases respectively by about 2- and 10-fold. This enzyme is not inducible during larval and postlarval stages of R. pipiens. However, cytochrome P4501A1 (CYPIA1 gene product) is inducible by beta-naphthoflavone in all these species. Both CYPIA and CYPIIB genes are expressed, as determined by the catalysis of their protein products, during larval, postlarval, and adult stages of R. pipiens. The concentration of P450 increases slightly during the postlarval stages until the adult stage, ready to migrate to land, is reached. This increase seems to be mostly due to 2B1-type cytochrome P450 as judged by a large increase in aldrin epoxidase but not of 7-ethoxyresorufin O-deethylase activity. It is hypothesized that the evolution of true terrestrialness, and not the evolution of air-breathing lungs alone, is required for the transcriptional activation of CYPIIB gene by PB.