A quantitative pharmacological analysis of some excitatory amino acid receptors in the mouse neocortex in vitro.

1. The effects of 2-amino-5-phosphonovalerate and kynurenate, either alone or in combination, were tested on responses evoked by the excitatory amino acid agonists quinolinate, ibotenate, N-methyl-D-aspartate and N-methyl-DL-aspartate by use of an in vitro preparation of mouse neocortex and artificial cerebrospinal fluid nominally free of magnesium. 2. Schild plots for 2-amino-5-phosphonovalerate, using each of the excitatory amino acids, were linear and had a slope not significantly different from one. The apparent pA2 values for 2-amino-5-phosphonovalerate using each of the excitatory amino acids were 4.98 (quinolinate), 5.00 (N-methyl-DL-aspartate), 4.92 (N-methyl-D-aspartate) and 5.05 (ibotenate). The apparent pA2 obtained using ibotenate was distinct from that of N-methyl-D-aspartate but there were no significant differences between pA2 estimates for quinolinate, N-methyl-D-aspartate or N-methyl-DL-aspartate. 3. Schild plots for kynurenate, using each of the excitatory amino acids, were linear and had a slope of 1.36 +/- 0.03, significantly greater than one. The estimated apparent pA2 values for kynurenate were 3.65 (quinolinate), 3.71 (N-methyl-DL-aspartate), 3.65 (N-methyl-D-aspartate) and 3.89 (ibotenate). The apparent pA2 obtained using ibotenate was distinct from that of the other agonists. 4. Experiments using combinations of 2-amino-5-phosphonovalerate and kynurenate indicated that both antagonists apparently acted competitively at receptors activated by ibotenate or by quinolinate. 5. These results indicate that ibotenate acts at a site distinct form that of quinolinate, N-methyl-D-aspartate and N-methyl-DL-aspartate.