Glutamate agonists and [3H]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 the Ca(2+)-dependent and independent releases of [3H]GABA from rat coronal hippocampal slices were studied in a superfusion system. The Ca(2+)-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 Ca(2+)-free medium. The release evoked by QA in Ca(2+)-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)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. The inhibition of MK-801 was slightly diminished and that of CNQX totally abolished in Ca(2+)-free medium. Verapamil inhibited the QA-activated release in both Ca(2+)-containing and Ca(2+)-free media. The effect of QA but not that of AMPA was blocked in Ca(2+)-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+ form intracellular stores.
Janáky
R
R
Department of Biomedical Sciences, University of Tampere, Finland.
Varga
V
V
Saransaari
P
P
Oja
S S
SS
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000502:physiology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005971:Glutamates; D011810:Quinoxalines; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D016318:Quisqualic Acid; D007608:Kainic Acid; D002118:Calcium