RELEASE OF ENDOGENOUS GLUTAMIC AND ASPARTIC ACIDS FROM CEREBROCORTEX SYNAPTOSOMES AND ITS MODULATION THROUGH ACTIVATION OF A GAMMA-AMINOBUTYRIC ACIDB (GABA-B) RECEPTOR SUBTYPE

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 Ca2+-dependent. Exogenous GABA inhibited the K+-evoked overflow of GLU (EC50 2.8 muM) and ASP (EC50 2.7 muM). The effect of GABA was mimicked by the GABA(B) receptor agonist (-)-baclofen (EC50 2.0 muM for GLU and 1.3 muM for ASP release) but not by the GABA(A) receptor agonist muscimol, up to 100 muM. 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 muM. 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.