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Effect of Nipecotic Acid, a γ‐Aminobutyric Acid Transport Inhibitor, on the Turnover and Release of γ‐Aminobutyric Acid in Rat Cortical Slices
Author(s) -
Szerb John C.
Publication year - 1982
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1982.tb07970.x
Subject(s) - nipecotic acid , endogeny , aminobutyric acid , stimulation , tetrodotoxin , gamma aminobutyric acid , aminooxyacetic acid , chemistry , metabolite , biochemistry , gabaergic , biophysics , neurotransmitter , biology , endocrinology , receptor , enzyme
To see the effect of a γ‐aminobutyric acid GABA uptake inhibitor on the efflux and content of endogenous and labeled GABA, rat cortical slices were first labeled with [ 3 H]GABA and then superfused in the absence or presence of 1 m M nipecotic acid. Endogenous GABA released or remaining in the slices was measured with high performance liquid chromatography, which was also used to separate [ 3 H]GABA from its metabolites. In the presence of 3 m M K + , nipecotic acid released both endogenous and [ 3 H]GABA, with a specific activity four to five times as high as that present in the slices. The release of labeled metabolite(s) of [ 3 H]GABA was also increased by nipecotic acid. The release of endogenous GABA evoked by 50 m M K + was enhanced fourfold by nipecotic acid but that of [ 3 H]GABA was only doubled when expressed as fractional release. In a medium containing no Ca 2+ and 10 m M Mg 2+ , the release evoked by 50 m M K + was nearly suppressed in either the absence or the presence of nipecotic acid. In the absence of nipecotic acid electrical stimulation (bursts of 64 Hz) was ineffective in evoking release of either endogenous or [ 3 H]GABA, but in the presence of nipecotic acid it increased the efflux of endogenous GABA threefold, while having much less effect on that of [ 3 H]GABA. Tetrodotoxin (TTX) abolished the effect of electrical stimulation. Both high K + and electrical stimulation increased the amount of endogenous GABA remaining in the slices, and this increase was reduced by omission of Ca 2+ or by TTX. The results suggest that uptake of GABA released through depolarization is of major importance in removing GABA from extracellular spaces, but the enhancement of spontaneous release by nipecotic acid may involve intracellular heteroexchange. Depolarization in the presence of Ca 2+ leads to an increased synthesis of GABA, in excess of its release, but the role of this excess GABA remains to be established.