Pende M, Lanza M, Bonanno G, Raiteri M
Instituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Brain Res. 1993 Feb 26;604(1-2):325-30. doi: 10.1016/0006-8993(93)90384-y.
The depolarization-evoked release of endogenous glutamate (GLU) and -aspartate (ASP) and its modulation mediated by gamma-aminobutyric acid (GABA) heteroreceptors was investigated in superfused rat cerebrocortical synaptosomes. Exposure to 12 mM K+ enhanced the release of GLU and ASP. The K(+)-evoked overflow of both amino acids was largely Ca(2+)-dependent. Exogenous GABA inhibited the K(+)-evoked overflow of GLU (EC50 2.8 microM) and ASP (EC50 2.7 microM). The effect of GABA was mimicked by the GABAB receptor agonist (-)-baclofen (EC50 2.0 microM for GLU and 1.3 microM for ASP release) but not by the GABAA receptor agonist muscimol, up to 100 microM. Accordingly, the GABA-induced inhibition of GLU and ASP release was not affected by the GABAA receptor antagonists, bicuculline or picrotoxin, but was antagonized by the GABAB receptor antagonist, 3-amino-propyl(diethoxymethyl)phosphinic acid (CGP 35348). The GABA effect was, however, insensitive to another GABAB receptor antagonist, phaclofen, up to 1,000 microM. It can be concluded that GABA heteroreceptors of the GABAB type regulating the depolarization-evoked release of GLU and ASP are present on cortical GLU/ASP-releasing nerve terminals. These receptors may be classified as a phaclofen-insensitive GABAB receptor subtype.
在灌流的大鼠大脑皮质突触体中，研究了去极化诱发的内源性谷氨酸（GLU）和天冬氨酸（ASP）释放及其由γ-氨基丁酸（GABA）异源受体介导的调节作用。暴露于12 mM K +可增强GLU和ASP的释放。两种氨基酸的K（+）诱发的溢出在很大程度上依赖于Ca（2+）。外源性GABA抑制K（+）诱发的GLU（EC50 2.8 microM）和ASP（EC50 2.7 microM）溢出。GABAB受体激动剂（-）-巴氯芬模拟了GABA的作用（GLU释放的EC50为2.0 microM，ASP释放的EC50为1.3 microM），但高达100 microM的GABAA受体激动剂蝇蕈醇则没有这种作用。因此，GABA诱导的GLU和ASP释放抑制不受GABAA受体拮抗剂荷包牡丹碱或印防己毒素的影响，但被GABAB受体拮抗剂3-氨基丙基（二乙氧基甲基）次膦酸（CGP 35348）拮抗。然而，高达1000 microM的另一种GABAB受体拮抗剂巴氯芬对GABA的作用不敏感。可以得出结论，调节GLU和ASP去极化诱发释放的GABAB型GABA异源受体存在于皮质GLU/ASP释放神经末梢上。这些受体可归类为对巴氯芬不敏感的GABAB受体亚型。
