Inhibition of [ 3H]γ-aminobutyric acid release by kainate receptor activation in rat hippocampal synaptosomes

Abstract

We studied the modulation of γ-aminobutyric acid (GABA) release by activation of kainate receptor in rat whole hippocampal synaptosomes. Kainate (10–300 μM) inhibited [ 3H]GABA release in a concentration-dependent manner with an EC 50 of 25 μM. This effect of kainate (30 μM) was prevented by the ionotropic non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) and by the selective kainate receptor antagonist 5-nitro-6,7,8,9-tetrahydrobenzo( g)indole-2,3-dione-3-oxime (NS-102, 10 μM), but not by the selective non-competitive AMPA receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5 H-2,3-benzodiazepine (GYKI 52466, 100 μM). Other kainate receptor agonists, such as domoic acid (0.3–10 μM) and (2 S,4 R)-4-methylglutamic acid (MGA, 0.3–3 μM), also inhibited [ 3H]GABA release in a concentration-dependent manner with EC 50 values of 4.0 μM and 0.90 μM, respectively, whereas α-amino-3-hydroxy-5-methyl-4-oxazolepropionate (AMPA, 10–100 μM) was devoid of effect. These inhibitory effects of both domoic acid (3 μM) and MGA (1 μM) were antagonized by CNQX (10 μM). These results indicate that GABA release can be modulated directly by presynaptic high-affinity kainate heteroreceptors. © 1997 Elsevier Science B.V. All rights reserved.