EFFECT OF GABACULINE ON METABOLISM AND RELEASE OF GAMMA-AMINOBUTYRIC-ACID IN SYNAPTOSOMES

Synaptosomes isolated from mouse brain were incubated with [14C]glutamate and [3H]γ-aminobutyric acid ([3H]GABA), and then [14C]GABA (newly synthesized GABA) and [3H]GABA (newly captured GABA) in the synaptosomes were analysed. (1) the [3H]GABA was rapidly degraded in the synaptosomes, (2) when the synaptosomes were treated with gabaculine (a potent inhibitor of GABA aminotransferase), the degradation of [3H]GABA was strongly inhibited, (3) the gabaculine treatment brough about a significant increase in Ca2+-independent release of [3H]GABA with no effect on Ca2+-dependent release, (4) no effects of gabaculine on degradation and release of [14C]GABA were observed. The results indicate that there are at least two pools of GABA in synaptosomes and support the possibilities that GABA taken up into a pool which is under the influence of GABA aminotransferase is released Ca2+-independently and that GABA synthesized in another pool which is not under the influence of GABA aminotransferase is released Ca2+-dependently. © 1990 Plenum Publishing Corporation.