Is the concentration of gamma-aminobutyric acid in the nerve terminal regulated via product inhibition of glutamic acid decarboxylase?
Fractions of synaptosomes were used to study the regulation of gamma-aminobutyric acid (GABA) synthesis. The isolated synaptosomes were superfused in media of various compositions. [3H]GABA and GABA released into the medium or remaining in the synaptosomes were analyzed by liquid scintillation and HPLC techniques. Different conditions, designed to increase the GABA efflux rate were used: the rate of superfusion was varied and the concentrations of K+ and Ca2+ were altered. Stimulation of GABA efflux was paralleled with an increased synthesis of GABA, since, in spite of the increased GABA efflux, a relatively constant intraterminal level was found. The findings suggest that the intraterminal concentration of GABA and thus also its synthesis is regulated via product inhibition. In addition, [3H]GABA, exogenous, and GABA, endogenous, responded to external stimulae (Ca2+, veretradine, various GABA concentrations and the glutaminase inhibitor diazo-nor-leucine) in a way which was compatible with them being localized in and/or released from different compartments.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D066298:In Vitro Techniques; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D014701:Veratridine; D005968:Glutamate Decarboxylase; D002118:Calcium