Oligopeptides as substrates and inhibitors for a new constitutive nitric oxide synthase from rat cerebellum

A new constitutive nitric oxide synthase (NOS) that utilizes both L-arginine and bradykinin (BK) as substrates has been purified from rat cerebellum. This NOS is calmodulin-dependent with L-arginine, but calmodulin-independent with BK. Peptide products obtained using BK and a related nonapeptide as substrates were isolated and sequenced. Both N- and C-terminal arginines of BK are oxidized to citrullines by this enzyme. With BK as substrate NOS activity is competitively inhibited by N-G-methyl-, N-G-nitro-L-arginines, and a BK receptor antagonist. Our results suggest that oligopeptide-utilizing NOS may occur in other tissues, and show for the first time that oligopeptides can function as substrates or inhibitors of NOS. (C) 1996 Academic Press, Inc.