Modulation of GABA release by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and N-methyl-D-aspartate receptors in matrix-enriched areas of the rat striatum.

Article date: 1992/10/1

PubMed ID: 1280348

Journal name: Neuroscience (ISSN: 0306-4522)


Using a new in vitro superfusion device, the release of preloaded [3H]GABA was examined in microdiscs of tissues taken from sagittal slices in matrix-enriched areas of the rat striatum. Potassium (9 mM, 15 mM) stimulated the release of [3H]GABA in a concentration- and calcium-dependent manner and the veratridine (1 microM)-evoked release of [3H]GABA was completely abolished in the presence of tetrodotoxin (1 microM). The selective glutamatergic agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (1 mM) enhanced the potassium-evoked release of [3H]GABA as well as the basal outflow of [3H]GABA. This latter effect was found to be calcium-dependent, partially diminished by tetrodotoxin (1 microM), completely blocked by 6,7-dinitro-quinoxaline-2,3-dione (0.1 mM), which is generally used as an antagonist of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors, but not affected by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK801, 10 microM), a specific antagonist of N-methyl-D-aspartate receptors. Similarly, N-methyl-D-aspartate (1 mM) enhanced both the potassium (9 mM) and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (1 mM)-evoked release of [3H]GABA but when used alone, due to the presence of magnesium in the superfusion medium, was ineffective on the basal efflux of [3H]GABA. A stimulatory effect of N-methyl-D-aspartate (1 mM) on the basal outflow of [3H]GABA was observed, however, when magnesium was omitted from the superfusion medium. The stimulatory effect of N-methyl-D-aspartate (1 mM) observed in the presence of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate was not potentiated by glycine (1 microM, in the presence of strychnine 1 microM) and the N-methyl-D-aspartate-evoked response seen in the absence of magnesium was not enhanced by D-serine (1 mM), suggesting that endogenous glycine is already acting on N-methyl-D-aspartate receptors. In fact, in the absence of magnesium, 7-chloro-kynurenate (1 mM) completely abolished the stimulatory effect of N-methyl-D-aspartate on the release of [3H]GABA confirming that under our conditions, the glycine site of the N-methyl-D-aspartate receptor is saturated. N-methyl-D-aspartate-evoked responses were all blocked by MK801 (10 microM). Finally, the N-methyl-D-aspartate-evoked response seen in the absence of magnesium was markedly reduced in the presence of tetrodotoxin (1 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

Author List: Galli T, Desce J M, Artaud F, Kemel M L, Chéramy A, Glowinski J

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Quinoxalines; Receptors, N-Methyl-D-Aspartate; Ibotenic Acid; Tetrodotoxin; gamma-Aminobutyric Acid; FG 9041; Dizocilpine Maleate; Veratridine; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Potassium; Glycine;

Mesh terms: Animals; Corpus Striatum/drug effects; Dizocilpine Maleate/pharmacology; Glycine/pharmacology; Histocytochemistry; Ibotenic Acid/analogs & derivatives; Male; Nerve Endings/drug effects; Perfusion; Potassium/pharmacology; Quinoxalines/pharmacology; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate/drug effects; Synapses/drug effects; Synaptosomes/metabolism; Tetrodotoxin/pharmacology; Veratridine/pharmacology; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; gamma-Aminobutyric Acid/metabolism;

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