Glutamate agonists and [3H]GABA release from rat hippocampal slices: Involvement of metabotropic glutamate receptors in the quisqualate-evoked release |
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Authors: | R Janáky V Varga Pirjo Saransaari S S Oja |
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Institution: | (1) Tampere Brain Research Center, Department of Biomedical Sciences, University of Tampere, Box 607, SF-33101 Tampere, Finland |
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Abstract: | The effects of glutamate agonists and their selective antagonists on the Ca2+-dependent and independent releases of 3H]GABA from rat coronal hippocampal slices were studied in a superfusion system. The Ca2+-dependent release evoked by glutamate, kainate and N-methyl-D-aspartate (NMDA) gradually declined with time despite the continuous presence of the agonists. Quisqualate (QA) caused a sustained release which exhibited no tendency to decline within the 20-min period of stimulation. This release was enhanced in Ca2+-free medium. The release evoked by QA in Ca2+-containing medium was significantly inhibited by (+)-5-methyl-10,11-dihydro-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 (RS)- -amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. The inhibition of MK-801 was slightly diminished and that of CNQX totally abolished in Ca2+-free medium. Verapamil inhibited the QA-activated release in both Ca2+-containing and Ca2+-free media. The effect of QA but not that of AMPA was 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 partly by activation of metabotropic receptors and mobilization of Ca2+ from intracellular stores. |
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Keywords: | GABA release quisqualate glutamate receptors metabotropic receptors hippocampal slices |
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