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.