BARBITURATE-INDUCED EXPRESSION OF NEURONAL NITRIC-OXIDE SYNTHASE IN THE RAT CEREBELLUM

Neuronal nitric oxide synthase (nNOS) is known to share some structura l and functional similarities with the cytochrome P450 mixed function oxidase system. Unlike P450, it does not require a second enzyme, redu ctase, to transfer electrons. This characteristic is similar to P450(B M-3) of Bacillus megaterium. P450(BM-3) and certain mammalian subfamil ies of P450, such as P4502B, are known to be induced by phenobarbital (PB), and these P450s share a consensus sequence called the Barbie box . Because of the similarities nNOS shares with P450(BM-3) and other ma mmalian P450s, we have examined whether nNOS also responds to PB treat ment. We have used semi-quantitative PCR, Western blot analysis, a fun ctional assay, and immunohistochemistry in order to answer this questi on. These data show a threefold increase in nNOS mRNA expression, more modest nNOS protein and activity induction, and no discernible change s in localization of nNOS within the cerebellum following PB treatment .