Enhancement of endogenous GABA release from rat synaptosomal preparations is mediated by α2-adrenoceptors pharmacologically different from α2-autoreceptors

Abstract The effects of various adrenergic agents on the release of endogenous γ-aminobutyric acid (GABA) and of [ 3 H]GABA were studied in superfused synaptosomal preparations from rat hippocampus. Noradrenaline (NA) enhanced in a concentration-dependent way the release of endogenous GABA but did not affect the release of the radioactive amino acid. The effect of NA was mimicked by the α 2 -adrenoceptor agonist, clonidine, but not by the α 1 -agonist, phenylephrine. Accordingly, NA was antagonized by the α 2 -adrenoceptor antagonist, yohimbine, but not by the α 1 -antagonist, prazosin. Both (+)-mianserin and (-)-mianserin, used as α 2 -adrenoceptor blockers, counteracted the NA-evoked release of endogenous GABA. The results suggest that GABA released from hippocampus crude synaptosomes is modulated by α 2 -adrenoceptors pharmacologically different from the α 2 -autoreceptors that modulate NA release and previously found to be blocked by (+)-mianserin but not by the (-)enantiomer (Raiteri et al., 1983).