GLUTAMATE AGONISTS AND [H-3] GABA RELEASE FROM RAT HIPPOCAMPAL SLICES- INVOLVEMENT OF METABOTROPIC GLUTAMATE RECEPTORS IN THE QUISQUALATE-EVOKED RELEASE

The effects of glutamate agonists and their selective antagonists on t he Ca2+-dependent and independent releases of [H-3]GABA from rat coron al hippocampal slices were studied in a superfusion system. The Ca2+-d ependent release evoked by glutamate, kainate and N-methyl-D-aspartate (NMDA) gradually declined with time despite the continuous presence o f the agonists. Quisqualate (QA) caused a sustained release which exhi bited no tendency to decline within the 20-min period of stimulation. This release was enhanced in Ca2+-free medium. The release evoked by Q A in Ca2+-containing medium was significantly inhibited by -10,11-dihy dro-5H-dibenzo(a,d)cyclohept-5,10-imine hydrogen maleate (MK-801) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), showing that QA activates NMDA receptors directly or indirectly through pha-amino-3-hydroxy-5-m ethyl-4-isoxazolepropionate (AMPA) receptors. The inhibition of MK-801 was slightly diminished and that of CNQX totally abolished in Ca2+-fr ee medium. Verapamil inhibited the QA-activated release in both Ca2+-c ontaining and Ca2+-free media. The effect of QA but not that of AMPA w as blocked in Ca2+-free medium by L(+)-2-amino-3-phosphonopropionate ( L-AP3), a selective antagonist of the metabotropic glutamate receptor. It is suggested that the sustained release of GABA is also mediated p artly by activation of metabotropic receptors and mobilization of Ca2 from intracellular stores.