Article date: 1991/12/1
PubMed ID: 1684816
Journal name: The Journal of pharmacology and experimental therapeutics (ISSN: 0022-3565)
The effects of gamma-aminobutyric acid (GABA) and of various GABA receptor agonists and antagonists on the calcium-dependent depolarization-evoked release of somatostatin (SRIF) from rat cerebrocortex synaptosomes have been studied by a superfusion technique. GABA (0.3-30 microM) decreased the K+ (15 mM)-evoked overflow of SRIF-like immunoreactivity (SRIF-LI) in a concentration-dependent manner (EC50 = 1.3 microM; maximal inhibition, 45% reached at 10 microM GABA). The effect of the amino acid was insensitive to the GABAA receptor antagonist bicuculline. Accordingly, the K(+)-evoked SRIF-LI release was not affected by muscimol, a GABAA receptor agonist, up to 100 microM. The effect of GABA was mimicked by the GABAB receptor agonist (-)-baclofen (EC50 = 1.2 microM; maximal effect, about 45% reached at 10 microM). The effect of baclofen was stereoselective, the (+)-enantiomer being inactive up to 100 microM. The inhibition of SRIF-LI release brought about by GABA was sensitive to the GABAB receptor antagonists 2-hydroxy-saclofen and CGP 35348 [3-aminopropyl(diethoxymethyl)phosphinic acid]. Also, the effect of (-)-baclofen was antagonized by CGP 35348 (IC50 = 4.8 microM). It is concluded that GABA can inhibit the depolarization-evoked release of SRIF by activating receptors which are located on SRIF-releasing nerve terminals and belong to the GABAB type.
Author List: Bonanno G, Gemignani A, Fedele E, Fontana G, Raiteri M
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: Nipecotic Acids; Receptors, GABA-A; Somatostatin; gamma-Aminobutyric Acid; N-(4,4-diphenyl-3-butenyl)nipecotic acid; Baclofen; Potassium;
Mesh terms: Animals; Baclofen/pharmacology; Cerebral Cortex/secretion; Kinetics; Male; Nerve Endings/secretion; Nipecotic Acids/pharmacology; Potassium/pharmacology; Rats; Rats, Inbred Strains; Receptors, GABA-A/physiology; Somatostatin/immunology; Synaptosomes/drug effects; gamma-Aminobutyric Acid/pharmacology;