Blockade by N-methylhydroxylamine or activation of guanylate cyclase and elevations of guanosine 3′,5′-monophosphate levels in nervous tissues

Abstract

Hydroxylamine and N-methylhydroxylamine prevented the activation of soluble guanylate cyclase by the endogenous activator as well as by nitroso compounds such as N-methyl- N′-nitro- N-nitroguanidine or nitroprusside, while the other derivaties of hydroxylamine were ineffective. Hydroxylamine and N-methylhydroxylamine did not alter the basal guanylate cyclase activity of purified enzyme preparations. Kinetics analysis indicated that N-methylhydroxylamine competes with N-methyl- N′nitro- N-nitrosuguanidine for guanylate cyclase. The activation of guanylate cyclase by N-methyl- N′-nitro- N-nitrosoguanidine and its inhibition by N-methylhydroxylamine were reversible reactions. These efects of N-methyl- N′-nitro- N-nitrosoguanine and N-methylhydroxylamine were observed with guanylate cyclase from other tissues. N-Methylhydroxylamine preveneed the increase of guanosine 3′,5′-monophosphate (cyclic GMP) levels in cerebellar slices of guinea pig by N-methyl- N′-nitro- N-nitroguanidine, veratridine and adenosine, while the elevalations of adenosine 3′,5′-monophosphate by these agents were not affected. N-Methylhyroxylamine also blocked the increased of cyclic GMP levels by carbachol, prostaglandin E 1 and N-methyl- N′-nitro- N-nitrosoguanidine in neuroblastoma N1E 115 cells. Thus N-methylhydroxylamine prevents the activation of guanylate cyclase and the increased synthesis of cyclic GMP in responses to transmitters without blocking the synthesis of cyclic GMP via basal enzyme activity.