Blockade by N-methylhydroxylamine of activation of guanylate cyclase and elevations of guanosine 3',5'-monophosphate levels in nervous tissues.
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-nitrosoguanidine or nitroprusside, while 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-nitrosoguanidine 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 effects of N-methyl-N'-nitro-N-nitrosoguanidine and N-methylhydroxylamine were observed with guanylate cyclase from other tissues. N-Methylhydroxylamine prevented the increase of guanosine 3',5'-monophosphate (cyclic GMP) levels in cerebellar slices of guinea pig by N-methyl-N'-nitro-N-nitrosoguanidine, veratridine and adenosine, while the elevations  of adenosine 3',5'-monophosphate by these agents were not effected. N-Methylhydroxylamine also blocked the increases of cyclic GMP levels by carbachol, prostaglandin E1 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 response to transmitters without blocking the synthesis of cyclic GMP via basal enzyme activity.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism*; D006898:Hydroxylamines / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009603:Nitroso Compounds / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D006898:Hydroxylamines; D009603:Nitroso Compounds; D006162:Guanylate Cyclase; D006152:Cyclic GMP; C018338:N-methylhydroxylamine