A comparison of excitatory amino acid antagonists acting at primary afferent C fibres and motoneurones of the isolated spinal cord of the rat

1 The potency of 7 excitatory amino acid antagonists has been measured at kainate receptors on primary afferent C fibres using isolated dorsal roots from immature rats. Two of the compounds were tested as antagonists of excitant amino acids at motoneurones using isolated hemisected spinal cord preparations. 2 Mean dose‐ratios for antagonism of kainate at C fibres, produced by 1 mm antagonist in at least four preparations, ranged from 2.1 ± 0.5 (mean ± s.e.mean) with 2‐amino‐5‐phosphonopentanoate (AP5) to 17.6 ± 2.4 with 1‐(p‐bromobenzoyl)‐piperazine‐2, 3‐dicarboxylate (BBpzD). The rank order of potency of antagonists at C fibres was similar to that obtained previously for antagonism of kainate at motoneurones. 3 The potency of kynurenate as an antagonist of kainate at C fibres (apparent Kd 70 ± 4.3 μm (mean ± s.e.mean), n = 12) was significantly different (P < 0.005, Wilcoxon rank sum) from its potency at motoneurones (apparent Kd 164 ± 14 μm, n = 13). Kynurenate also was significantly (P < 0.025 Wilcoxon rank sum) more potent at antagonizing kainate‐than quisqualate (apparent Kd 258 ± 28 μm, n = 12)‐induced depolarization of motoneurones. 4 Kynurenate and BBpzD (0.25, 1.0 and 4.0 mm) were compared as antagonists of N‐methyl‐d‐aspartate (NMDA) at motoneurones and the slope of the Gaddum‐Schild plot for kynurenate was markedly greater than 1 (2.01 ± 0.22, 95% confidence limits). A greater than additive antagonism of NMDA‐induced depolarizations was produced by combinations of kynurenate with, either AP5, or magnesium ions. 5 The results suggest that the kainate receptor on C fibres may be different from the kainate receptor on motoneurones and that antagonism of NMDA‐induced depolarization by kynurenate may not be entirely competitive.