The effects of the glutamate receptor antagonist gamma-D-glutamylaminomethyl sulfonic acid (GAMS) on inward currents induced by bath application of kainic acid (KA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) were studied with single-electrode voltage clamp methods in Xenopus oocytes injected 3-5 days previously with mRNA from the brain of E16-17 chick embryos. Both AMPA and KA induced smooth inward currents, with Hill coefficients of 1.5 (AMPA) and 2.1 (KA). GAMS, at concentrations up to 1 mM, produced no reliable antagonism of AMPA-induced currents but showed a consistent, dose-dependent and reversible antagonism of KA-induced responses; the slope of the Schild plot was 0.76 and the pA2 value 4.32. In the presence of GAMS, however, the Hill coefficient for AMPA is reduced significantly and approaches unity, suggesting that AMPA interacts with both KA and AMPA binding sites on chick brain glutamate receptors. The selectivities of three quinoxalinedione antagonists (6,7-dinitroquinoxaline-2,3-dione [DNQX], 6-cyano-7- nitroquinoxaline-2,3-dione [CNQX] and 6-nitro-7-sulfamoyl-benzo(F)quinoxaline-2,3-dione [NBQX]) were then compared with that shown by GAMS. DNQX, CNQX and NBQX all blocked the effects of both KA and AMPA completely, competitively, reversibly and dose-dependently, with Schild-plot slopes very close to 1.0. Against AMPA, observed pA2 values were 6.58 for DNQX, 6.43 for CNQX and 6.77 for NBQX. Against KA, pA2 values were 6.42 for DNQX, 6.56 for CNQX and 7.21 for NBQX.(ABSTRACT TRUNCATED AT 250 WORDS)