GABA induced changes in acetylcholine release from slices of guinea-pig brain

Summary The effect of GABA on acetylcholine (ACh) release was investigated on superfused slices of guinea-pig cerebral cortex (CC), caudate nucleus (CN), tuberculum olfactorium and brain stem.GABA (1–6×10^–3 mol/l) increased the spontaneous and KCl-evoked ACh overflow in CC and CN, reduced the electrically-evoked release in all areas tested (most evidently in CC and CN) and lowered the threshold of electric stimulation-induced ACh release in CC. These effects were also caused by 3-amino-1-propane sulphonic acid (1×10^–3mol/l) and ethanolamine-O-sulphate (2×10^–4mol/l), were reduced by bicuculline (1×10^–4mol/l) and fully antagonized by picrotoxin (8×10^–5mol/l), but they were not influenced by phentolamine, methysergide, spiroperidol or strychnine.Tetrodotoxin (TTX) (5×10^–7mol/l) blocked the facilitation of spontaneous ACh release by GABA only when the slices were perfused with normal Krebs solution, but not when perfused with a KCl-enriched medium. These results suggest that GABA affects the cholinergic transmitter release through bicuculline- and picrotoxin-sensitive receptors, showing low affinity toward the agonist. Moreover GABA modulation of resting ACh release requires action potentials only in normal [K⁺]₀, but not in high [K⁺]₀, suggesting that GABA-receptive sites are located at cholinergic terminals.