Abstract:The activation of kainic acid and quisqualic acid receptors in cultured cerebellar granule cells stimulated the release of preaccumulatedd‐[3H]aspartate. The effect of kainate could be distinguished from that of quisqualate by its sensitivity to the antagonists kynurenic acid and 2,3‐cis‐piperidine dicarboxylic acid. At a concentration of kainic acid (50 μM) close to its half‐maximal releasing effect, simultaneous addition of quisqualic acid (10–50 μM) resulted in a significant dose‐dependent inhibition of the kainate‐induced component ofd‐[3H]aspartate release, which was monitored by the progressive decrease in sensitivity of the evoked release to kynurenic acid. In contrast, when kainic acid was used at a subeffective concentration (10 μM), addition of low doses of quisqualate (2–5 μM) resulted in a synergistic effect ond‐[3H]aspartate release. Under these conditions, the effect of the two agonists was sensitive to kynurenic acid. Kainic acid (50–100 μM) also caused a dose‐dependent, kynurenic acid‐sensitive accumulation of cyclic GMP (cGMP) in granule cell cultures. Quisqualic acid was, by itself, ineffective and prevented, in a dose‐dependent manner, the kainate‐induced cGMP formation (IC50= 5 μM). Finally, the guanylate cyclase activator sodium nitroprusside greatly enhanced cGMP formation but had no effect ond‐[3H]aspartate release. Together, these results demonstrate the existence of complex interactions between quisqualic and kainic acids and indicate that the effects of the two glutamate agonists ond‐[3H]aspartate release a