Article date: 1991/1/25
PubMed ID: 2054596
Journal name: Brain research (ISSN: 0006-8993)
The effect of gamma-aminobutyric acid (GABA) on the release of [3H]acetylcholine [( 3H]ACh) from human cerebral cortex nerve terminals was investigated using synaptosomes prepared from neurosurgical specimens (which had to be removed to reach deeply located tumors) prelabeled with [3H]choline and exposed in superfusion to varying concentrations of GABA. The amino acid (3-100 microM) increased in a concentration-dependent manner (maximal effect: 40%; EC50 = 14.7 microM) the release of [3H]ACh but not that of [3H]choline. The GABAA receptor agonist muscimol (up to 100 microM) did not increase significantly the release of [3H]ACh. Accordingly, the effect of GABA was insensitive to the GABAA receptor antagonist bicuculline. The release of [3H]ACh was not affected by the GABAB receptor agonist (-)-baclofen (100-300 microM). The GABA-induced [3H]ACh release was counteracted by two inhibitors of GABA uptake, N-(4,4-diphenyl-3-butenyl)nipecotic acid (SKF 89976A) and nipecotic acid. Moreover, the enhancing effect of GABA on [3H]ACh release was clearly Na+-dependent and was reduced by almost 90% in presence of 23 mM NaCl. The data indicate that, similarly to what had been observed in the rat, cholinergic nerve terminals in the human cerebral cortex possess a GABA transporter. Activation of this carrier brings about release of newly synthesized ACh. GABA and ACh might co-exist in some cerebrocortical nerve endings in the vertebrate brain, including man.
Author List: Bonanno G, Ruelle A, Andrioli G C, Raiteri M
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: Anticonvulsants; Carrier Proteins; GABA Plasma Membrane Transport Proteins; Membrane Proteins; Membrane Transport Proteins; Nerve Tissue Proteins; Nipecotic Acids; Organic Anion Transporters; nipecotic acid; Muscimol; gamma-Aminobutyric Acid; N-(4,4-diphenyl-3-butenyl)nipecotic acid; Proline; homoproline; Baclofen; Choline; Acetylcholine; Bicuculline;
Mesh terms: Acetylcholine/metabolism; Anticonvulsants/pharmacology; Baclofen/pharmacology; Bicuculline/pharmacology; Biotransformation; Carrier Proteins; Cerebral Cortex/cytology; Choline/metabolism; Female; GABA Plasma Membrane Transport Proteins; Humans; In Vitro Techniques; Male; Membrane Proteins; Membrane Transport Proteins; Middle Aged; Muscimol/pharmacology; Nerve Endings/drug effects; Nerve Tissue Proteins/metabolism; Nipecotic Acids/pharmacology; Organic Anion Transporters; Parasympathetic Nervous System/drug effects; Proline/analogs & derivatives; Synaptosomes/drug effects; gamma-Aminobutyric Acid/pharmacology;