In cultured striatal neurons, maximal [3H]GABA release stimulated by quisqualate (QA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) was 10-20 times smaller than that stimulated by kainate (KA), and we have previously reported that QA or AMPA competitively inhibited KA-evoked GABA release. Since the lectin concanavalin A (Con A) has been shown to inhibit QA receptor desensitization, the interaction between QA and KA was further studied in Con A-treated neurons. Con A dose-dependently and specifically potentiated QA- or AMPA-evoked [3H]GABA release, so that maximal responses of QA or AMPA were half of that of KA. The responses of these agonists were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) with similar apparent Ki values, indicating that they resulted from non-NMDA receptor activation. In Con A-treated neurons, QA and AMPA competitively inhibited the KA-induced GABA release. The apparent affinities of QA and AMPA in inhibiting the KA response were identical to their affinities in stimulating GABA release. Moreover, the maximal KA response measured in the presence of QA or AMPA was identical to that measured with KA alone. These results clearly indicate that to stimulate GABA release from Con A-treated striatal neurons, QA and AMPA behave as partial agonists of a receptor fully activated by KA. These results further support the hypothesis that QA, AMPA and KA act on a common receptor type in striatal neurons.