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The effect of chronic treatment with the GABA transaminase inhibitors gamma-vinyl-GABA and ethanolamine-O-sulphate on the in vivo release of GABA from rat hippocampus.

Authors: Qume, M  Whitton, PS  Fowler, LJ 
Citation: Qume M, etal., J Neurochem. 1995 May;64(5):2256-61.
Pubmed: (View Article at PubMed) PMID:7722510

The effects of chronic treatment with the specific, mechanism-based, irreversible inhibitors of 4-aminobutyrate aminotransferase (EC; GABA transaminase), ethanolamine O-sulphate (EOS), and 4-aminohexenoate [vigabatrin; gamma-vinyl-GABA (GVG)] on the extracellular concentrations of GABA in the hippocampus have been studied using in vivo microdialysis in conscious animals. Oral dosing [3 mg/ml of drinking water, giving doses of GVG of 194 +/- 38 mg/kg/day and of EOS of 303 +/- 42 mg/kg/day (mean +/- SD)] was followed by microdialysis at 2, 8, and 21 days. The basal outflow of GABA (in the range of approximately 1-2 pmol/30 microliters/30-min sample) after 2 and 8 days of treatment was not significantly different from that in control animals, but the 21-day treatment gave significant rises in the extracellular GABA concentration (up to approximately 6-8 pmol/30 microliters/30-min sample). Both inhibitors gave similar results. Depolarisation with 100 mM K+ gave large increases in GABA release in control (approximately 20-60 pmol/30 microliters/30-min sample) and treated animals. The 8- and 21-day-treated animals showed significant increases in the stimulated release compared with control animals (approximately 80-100 pmol/30 microliters/30-min sample). Excluding Ca2+ had no significant effect on either basal or stimulated release. The significant increases in K(+)-evoked release of GABA show that the increased intracellular pool of GABA is available for release, and this may be related to the anticonvulsant action of these compounds.


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CRRD Object Information
CRRD ID: 10046061
Created: 2015-07-06
Species: All species
Last Modified: 2015-07-06
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.