Nanomolar N(G)-nitroarginine inhibits NMDA-induced cyclic GMP formation in rat cerebellum.
The very large increases in cyclic GMP levels that occur in cerebellar slices in response to N-methyl-D-aspartate (NMDA) receptor agonists result from the synthesis of the guanylate cyclase activator, nitric oxide, from L-arginine. We show that an arginine analogue, L-NG-nitroarginine, inhibits the cyclic GMP response to NMDA in an arginine-sensitive manner. There were two components to the inhibition, IC50 values being 6 and 600 nM. L-NG-nitroarginine is most potent inhibitor of nitric oxide synthesis in the brain described so far. The dual-component inhibition may reflect the presence of two nitric oxide synthase enzymes which differ markedly in their sensitivity to this compound.
East
S J
SJ
Department of Physiology, University of Liverpool, U.K.
Garthwaite
J
J
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis*; D066298:In Vitro Techniques; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D051381:Rats
D019335:Nitroarginine; D016202:N-Methylaspartate; D001120:Arginine; D006152:Cyclic GMP