Presence of a gamma-aminobutyric acid (GABA) uptake system on cholinergic terminals of rat hippocampus: evidence for neuronal coexistence of acetylcholine and GABA?

The effect of gamma-aminobutyric acid (GABA) on the basal release of [3H]acetylcholine ([3H]ACh) was investigated using synaptosomes prepared from rat hippocampus and superfused after prelabeling with [3H]choline. Exogenous GABA added to the superfusion medium caused a long-lasting and concentration-dependent enhancement of the basal efflux of [3H]ACh. The effect of GABA was not antagonized by bicuculline or picrotoxin. Muscimol increased slightly but not significantly the release of [3H]ACh, whereas (+/-)-baclofen or (-)-baclofen were ineffective. The effect of GABA was counteracted by SK&F 89976A [N-(4,4-diphenyl-3-butenyl)-nipecotic acid], SK&F 100330A [N-(4,4-diphenyl-3-butenyl)-guvacine] and SK&F 100561 [N-(4,4-diphenyl-3-butenyl)-homo-beta-proline], three novel inhibitors of GABA uptake, but was unaffected by hemicholinium-3 or by beta-alanine. Nipecotic acid, a substrate-inhibitor of the GABA transporter, mimicked GABA and enhanced [3H]ACh release. The results indicate that a GABA transport system is present on cholinergic terminals.