We have used primary cultures of cerebellar granule cells to study the intracellular molecular processes elicited by the interaction of excitatory amino acids with specific membrane receptors. We have shown that at least two different dicarboxylic amino acids receptors are coupled with inositol phospholipid metabolism in primary cultures of cerebellar granule cells; one is sensitive to the stimulatory action of glutamate and aspartate and is preferentially antagonized by 2-amino-5-phosphonovalerate (APV); the other is activated by kainic acid and preferentially antagonized by cis, 2,3-piperidindicarboxylic acid (PDA). The activation of these sites by glutamate, asfertate and kainic acid also results in an enhanced formation of cGMP. The stimulatory action of glutamate and aspartate on cGMP is markedly influenced by the ionic composition of the incubation buffer and is potentiated by depolarizing stimuli. The action of kainic acid is independent of such parameters.
