GABA transaminase inhibitors enhance the release of endogenous GABA but decrease the release of beta-alanine evoked by electrical stimulation of slices of the rat medulla oblongata

Abstract

Slices of the rat medulla oblongata were superfused and electrically stimulated. The amount of endogenous GABA, beta-alanine and glutamate release from the slices was determined by high performance liquid chromatography with fluorometric detection. Inhibitors of GABA-transaminase (GABA-T), aminooxyacetic acid (10(-5) M), gamma-acetylenic GABA (10(-4) and 10(-3) M) and gabaculine (10(-5) M), enhanced the stimulus-evoked release of GABA and reduced that of beta-alanine, while no change was observed in the release of glutamate. These changes in amino acid release from the slices were accompanied by an increase in the content of GABA and a decrease in that of beta-alanine. The stimulus-evoked release of these amino acids was abolished by Ca2+-deprivation, in either the presence or absence of GABA-T inhibitors. These results suggest a modulatory role of GABA-T for synaptically releasable GABA and involvement of this enzyme in the synthesis of releasable beta-alanine.