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]gamma-amino-butyric 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 brought 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.
Asakura
T
T
Department of Biochemistry, Jikei University School of Medicine, Tokyo, Japan.
Matsuda
M
M
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008297:Male; D051379:Mice; D011188:Potassium / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D003509:Cyclohexanecarboxylic Acids; D005971:Glutamates; C012987:gabaculine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D011188:Potassium; D002118:Calcium