NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices.
Activation of N-methyl-D-aspartate (NMDA) receptors in rat cerebellum leads to the release of endothelium-derived relaxing factor, now identified as nitric oxide (NO), a stimulator of soluble guanylate cyclase. L-NG-monomethylarginine (L-NMMA), which blocks NO synthesis from L-arginine in several tissues, including a crude synaptosomal preparation from brain, inhibited the elevation of cyclic GMP induced by NMDA in rat cerebellar slices. D-NMMA was ineffective. L-Arginine, but not its D enantiomer, augmented the response to NMDA and reversed the inhibition by L-NMMA. The results indicate that stimulation of NMDA receptors results in the activation of the enzyme which catalyzes the formation of NO from L-arginine.
Garthwaite
J
J
Department of Physiology, University of Liverpool, U.K.
Garthwaite
G
G
Palmer
R M
RM
Moncada
S
S
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D066298:In Vitro Techniques; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP