Two distinct quisqualate receptor systems are present on striatal neurons

At concentrations at which it did not alter spontaneous release, quisqualate (QUIS) induced a dose-dependent (EC50, 0.5 microM) potentiation of KCl- or veratrine-evoked release of [3H]GABA from striatal neurons in primary culture. QUIS potentiation of KCl-evoked [3H]GABA release was mimicked by the selective agonist alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA), glutamate and kainate, and was blocked by kynurenic acid and gamma-D-glutamylglycine. QUIS also induced a dose-dependent (EC50, 0.2 microM) augmentation of [3H]inositol monophosphate production in striatal neurons. This action of QUIS was mimicked by glutamate, but not by AMPA nor by kainate. Furthermore, none of the antagonists tested (kynurenic acid, gamma-D-glutamylglycine, glutamic acid diethyl ester, and 4-aminophosphonobutanoic acid) could block QUIS-induced elevations in [3H]inositol monophosphate production. The results of the present study suggest that two QUIS receptor systems, distinguished on the basis of their pharmacological properties, may subserve specific roles in the regulation of striatal neuron function by excitatory amino acids.