Dual effects of NMDA-induced intracellular Ca2+ elevations on cGMP levels in cultured cerebellar granule neurons.

1. Cyclic GMP (cGMP) levels were markedly elevated by N-methyl-D-aspartate (NMDA) within 1-3 min of incubation, then gradually decreased with incubation time. 2. The NMDA-induced intracellular Ca2+ elevations showed maximal levels just after adding NMDA and were maintained for 60 min. 3. NMDA did not show augmentation of cGMP elevation with sodium nitroprusside (SNP), rather it decreased the SNP-induced cGMP elevation after exposure for 60 min. 4. The NMDA-induced elevation of cGMP was remarkably augmented with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX, 1mM), after 60 min of incubation.