Kainate produces concentration-dependent elevation of glutamate release but not cGMP levels in cultured neuron

1. Treatment of cultured cerebellar granule cells for 3 min with N-methyl-D-aspartate (NMDA) resulted in a concentration-dependent elevation of cyclic GMP. However, neither kainate (KA) nor NMDA produced a concentration-dependent elevation of this nucleotide after exposing cells to the agonist for 60 min. 2. Unlike the case for cGMP, both KA and NMDA produced concentration-dependent elevations of glutamate for 60 min incubation. 3. The NMDA-induced elevations of cGMP and glutamate were blocked by selective NMDA receptor antagonists. 4. The selective KA/α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, 6,7-nitroquinoxaline-2,3-dione (DNQX), blocked the KA-induced elevations of cGMP with 3-min exposures, but it augmented the response with 60-min exposures. However, the KA-induced release of glutamate was prevented by DNQX. 5. The KA/AMPA receptor antagonist, GYKI 52466, blocked all KA-induced responses regardless of the incubation times.