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-met hyl-D-aspartate (NMDA) resulted in a concentration dependent elevation of cyclic GMP. However, neither kainate (KA) nor NMDA produced a conc entration dependent elevation of this nucleotide after exposing cells to the agonist for 60 min. 2. Unlike the case for cGMP, both KA and NM DA 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 pha- amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagon ist, 6,7-nitroquinoxaline-2, 3-dione (DNQX), blocked the KA-induced el evations of cGMP with 3-min exposures, but it augmented the response w ith 60-min exposures. However, the KA-induced release of glutamate was prevented by DNQX. 5. The KA/AMPA receptor antagonist, GYKI 52466, bl ocked all KA-induced responses regardless of the incubation times.