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

Eur J Pharmacol. 1997 Apr 4;323(2-3):167-72. doi: 10.1016/s0014-2999(97)00043-5.


We studied the modulation of gamma-aminobutyric acid (GABA) release by activation of kainate receptor in rat whole hippocampal synaptosomes. Kainate (10-300 microM) inhibited [3H]GABA release in a concentration-dependent manner with an EC50 of 25 microM. This effect of kainate (30 microM) was prevented by the ionotropic non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and by the selective kainate receptor antagonist 5-nitro-6,7,8,9-tetrahydrobenzo(g)indole-2,3-dione-3-oxime (NS-102, 10 microM), 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 microM). Other kainate receptor agonists, such as domoic acid (0.3-10 microM) and (2S,4R)-4-methylglutamic acid (MGA, 0.3-3 microM), also inhibited [3H]GABA release in a concentration-dependent manner with EC50 values of 4.0 microM and 0.90 microM, respectively, whereas alpha-amino-3-hydroxy-5-methyl-4-oxazolepropionate (AMPA, 10-100 microM) was devoid of effect. These inhibitory effects of both domoic acid (3 microM) and MGA (1 microM) were antagonized by CNQX (10 microM). These results indicate that GABA release can be modulated directly by presynaptic high-affinity kainate heteroreceptors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Excitatory Amino Acid Agonists / pharmacology
  • GABA Antagonists / pharmacology*
  • Glutamates / pharmacology
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • In Vitro Techniques
  • Kainic Acid / analogs & derivatives
  • Kainic Acid / pharmacology
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Kainic Acid / drug effects*
  • Synaptic Transmission / physiology
  • Synaptosomes / metabolism*
  • gamma-Aminobutyric Acid / metabolism*


  • Excitatory Amino Acid Agonists
  • GABA Antagonists
  • Glutamates
  • Receptors, Kainic Acid
  • 4-methylglutamic acid
  • gamma-Aminobutyric Acid
  • domoic acid
  • Kainic Acid