IDENTIFICATION OF NITRIC OXIDE-SENSITIVE AND OXIDE-INSENSITIVE FORMS OF CYTOPLASMIC GUANYLATE-CYCLASE

Cytoplasmic, nitric oxide-activated guanylate cyclases are expressed i n many regions of the mammalian brain and are thought to participate i n functions as diverse as synaptogenesis and long-term potentiation. I n this study, we have characterized cytoplasmic guanylate cyclases in the nervous system of an invertebrate, the American lobster. Cytoplasm ic cyclase specific activity is higher in lobster nerve cord than in a ny other lobster tissue tested, and considerably higher than in typica l rat tissues (cerebellum, lung, and liver). However, nitric oxide don ors have minimal effects on lobster nerve cord cyclic GMP production, when applied either to intact tissue or to cytoplasmic extracts. Paral lel immunocytochemical studies, using an anti-cyclic GMP antibody, rev eal that only a small subset of lobster neurons responds to nitric oxi de with a significant elevation of cyclic GMP levels. HPLC analysis of nerve cord cytoplasm reveals two chromatographically separable cyclas es, a minor nitric oxide-sensitive form whose retention time is identi cal to that of the conventional mammalian enzyme and a more abundant n itric oxide-insensitive form that appears to be novel. The physiologic al function and phylogenetic distribution of this nitric oxide-insensi tive enzyme, and the signaling mechanisms that regulate its activity, are not known.