Dibutyryl cGMP augments kainate-induced elevation of intracellular calcium levels but not extracellular glutamate in cultured cerebellar granule neurons

These studies were designed to examine the effect of cGMP on glutamate neurotransmission. In primary cultures of cerebellar granule cells, the glutamate receptor agonists, N-methyl-D-aspartate (NMDA) and kainate, stimulate an elevation of intracellular calcium ([Ca²⁺](i)), the release of glutamate, the synthesis of nitric oxide (NO) and an increase in cGMP. Although it is clear that NMDA- and kainate-induced NO stimulates guanylyl cyclase, resulting in elevation of cGMP, it is unclear whether cGMP augments the NMDA-induced elevations of extracellular glutamate or [Ca²⁺](i) levels. We show that the membrane permeable cGMP analogue, dibutyryl cGMP (dBcGMP), slightly augments the NMDA-induced elevation of [Ca²⁺](i) and significantly augments the kainate-induced the elevation of [Ca²⁺](i) but augments neither NMDA- nor kainate-induced release of glutamate. These results suggest that cGMP has a role in maintaining the kainate and partially NMDA receptor activation. cGMP may not be involved in EAA-induced glutamate release.