Release of endogenous glutamic and aspartic acids from cerebrocortex synaptosomes and its modulation through activation of a γ-aminobutyric acid B (GABA B) receptor subtype

Abstract

The depolarization-evoked release of endogenous glutamate (GLU) and -aspartate (ASP) and its modulation mediated by γ-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 (EC 50 2.8 μM) and ASP (EC 50 2.7 μM). The effect of GABA was mimicked by the GABA B receptor agonist (−)-baclofen (EC 50 2.0 μM for GLU and 1.3 μM for ASP release) but not by the GABA A receptor agonist muscimol, up to 100 μM. Accordingly, the GABA-induced inhibition of GLU and ASP release was not affected by the GABA A receptor antagonists, bicuculline or picrotoxin, but was antagonized by the GABA B receptor antagonist, 3-amino-propyl(diethoxymethyl)phosphinic acid (CGP 35348). The GABA effect was, however, insensitive to another GABA B receptor antagonist, phaclofen, up to 1,000 μM. It can be concluded that GABA heteroreceptors of the GABA B 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 GABA B receptor subtype.