CHOLINERGIC NERVE-TERMINALS OF HUMAN CEREBRAL-CORTEX POSSESS A GABA TRANSPORTER WHOSE ACTIVATION INDUCES RELEASE OF ACETYLCHOLINE

The effect of gamma-aminobutyric acid (GABA) on the release of [H-3]acetylcholine ([H-3]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 [H-3]choline and exposed in superfusion to varying concentrations of GABA. The amino acid (3-100-mu-M) increased in a concentration-dependent manner (maximal effect: 40%; EC50 = 14.7-mu-M) the release of [H-3]ACh but not that of [H-3]choline. The GABA(A) receptor agonist muscimol (up to 100-mu-M) did not increase significantly the release of [H-3]ACh. Accordingly, the effect of GABA was insensitive to the GABA(A) receptor antagonist bicuculline. The release of [H-3]ACh was not affected by the GABA(B) receptor agonist (-)-baclofen (100-300-mu-M). The GABA-induced [H-3]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 [H-3]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.