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• W2048061420 endingPage "45" @default.
• W2048061420 startingPage "33" @default.
• W2048061420 abstract "The effect of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), a selective glutamate receptor agonist, on the release of previously incorporated [3H]GABA was examined in superfused striatal slices of the rat. The slices were loaded with [3H]GABA in the presence of β-alanine (1 mM) and superfused with Krebs-bicarbonate buffer containing nipecotic acid (0.1 mM) and aminooxyacetic acid (0.1 mM) to inhibit GABA uptake and metabolism. AMPA (0.01 to 3 mM) increased basal [3H]GABA outflow and nipecotic acid potentiated this effect. The [3H]GABA releasing effect of AMPA was an external Ca2+-dependent process in the absence but not in the presence of nipecotic acid. Cyclothiazide (0.03 mM), a positive modulator of AMPA receptors, failed to evoke [3H]GABA release by itself, but it dose-dependently potentiated the [3H]GABA releasing effect of AMPA. The AMPA (0.3 mM)-induced [3H]GABA release was antagonized by NBQX (0.01 mM) in a competitive fashion (pA2 5.08). The negative modulator of AMPA receptors, GYKI-53784 (0.01 mM) reversed the AMPA-induced [3H]GABA release by a non-competitive manner (pD′2 5.44). GYKI-53784 (0.01–0.1 mM) also decreased striatal [3H]GABA outflow on its own right, this effect was stereoselective and was not influenced by concomitant administration of 0.03 mM cyclothiazide. GYKI-52466 (0.03–0.3 mM), another negative modulator at AMPA receptors, also inhibited basal [3H]GABA efflux whereas NBQX (0.1 mM) by itself was ineffective in alteration of [3H]GABA outflow. The present data indicate that AMPA evokes GABA release from the vesicular pool in neostriatal GABAergic neurons. They also confirm that multiple interactions may exist between the agonist binding sites and the positive and negative modulatory sites but no such interaction was detected between the positive and negative allosteric modulators. Since GYKI-53784, but not NBQX, inhibited [3H]GABA release by itself, AMPA receptors located on striatal GABAergic neurons may be in sensitized state and phasically controlled by endogenous glutamate. It is also postulated that these AMPA receptors are located extrasynaptically on GABAergic striatal neurons." @default.
• W2048061420 created "2016-06-24" @default.
• W2048061420 creator A5006460217 @default.
• W2048061420 creator A5041609792 @default.
• W2048061420 creator A5051576670 @default.
• W2048061420 creator A5073880407 @default.
• W2048061420 date "2000-07-01" @default.
• W2048061420 modified "2023-09-27" @default.
• W2048061420 title "Negative allosteric modulators of AMPA-preferring receptors inhibit [3H]GABA release in rat striatum" @default.
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• W2048061420 doi "https://doi.org/10.1016/s0197-0186(00)00005-x" @default.
• W2048061420 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10781843" @default.
• W2048061420 hasPublicationYear "2000" @default.
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