Release of endogenous glutamic and aspartic acids from cerebrocortex synaptosomes and its modulation through activation of a gamma-aminobutyric acidB (GABAB) 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 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.
Pende
M
M
Instituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Lanza
M
M
Bonanno
G
G
Raiteri
M
M
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology*; D058787:GABA-A Receptor Antagonists; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007700:Kinetics; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000145:classification / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001224:Aspartic Acid; D001418:Baclofen; D001640:Bicuculline; D058787:GABA-A Receptor Antagonists; D005971:Glutamates; D018698:Glutamic Acid; D009943:Organophosphorus Compounds; D010852:Picrotoxin; D011189:Potassium Chloride; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C052329:phaclofen; C066430:CGP 35348