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A quantitative pharmacological analysis of some excitatory amino acid receptors in the mouse neocortex in vitro
Author(s) -
Burton N.R.,
Smith D.A.S.,
Stone T.W.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb10328.x
Subject(s) - quinolinate , excitatory postsynaptic potential , biochemistry , nmda receptor , ibotenic acid , excitatory amino acid antagonists , biology , quinolinic acid , quisqualic acid , amino acid , chemistry , receptor , glutamate receptor , endocrinology , kainic acid , tryptophan , central nervous system
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 pA 2 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 pA 2 obtained using ibotenate was distinct from that of N‐methyl‐ d ‐aspartate but there were no significant differences between pA 2 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 pA 2 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 pA 2 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 from that of quinolinate, N‐methyl‐ d ‐aspartate and N‐methyl‐ dl ‐aspartate.