Nitric oxide synthase inhibitor decreases the N-methyl-D-aspartate-induced release of glutamate in cerebellar granule neurons

These studies were designed to examine the effect of nitric oxide (NO) on glutamate neurotransmission. The glutamate receptor agonist, N-methyl-D-aspartate (NMDA), stimulates the release of glutamate, the synthesis of nitric oxide (NO) and an increase in cGMP in primary cultures of cerebellar granule cells. Although it is clear that NMDA-induced NO stimulates guanylyl cyclase, which results in elevation of cGMP, it is unclear whether NO or cGMP augments the NMDA-induced release of glutamate. We show that an NO synthase inhibitor, NG-monomethyl-L-arginine (MMA), decreases the NMDA-induced release of glutamate with complete blocking of cGMP elevations. However, these preventive effects of NO on glutamate release is abolished in low calcium buffer. These results suggest that NO has an important role in the release of glutamate in a calcium-dependent manner.