The Effect of Chronic Treatment with the GABA Transaminase Inhibitors γ-Vinyl-GABA and Ethanolamine-O-Sulphate on the In Vivo Release of GABA from Rat Hippocampus

Qume, M., Whitton, P.S. and Fowler, L.J. (2002) The Effect of Chronic Treatment with the GABA Transaminase Inhibitors γ-Vinyl-GABA and Ethanolamine-O-Sulphate on the In Vivo Release of GABA from Rat Hippocampus. Journal of Neurochemistry, 64 (5). p. 2256. 10.1046/j.1471-4159.1995.64052256.x.

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DOI: 10.1046/j.1471-4159.1995.64052256.x

Abstract

The effects of chronic treatment with the specific, mechanism-based, irreversible inhibitors of 4-aminobutyrate aminotransferase (EC 2.6.1.19; GABA transaminase), ethanolamine O-sulphate (EOS), and 4-aminohexenoate [vigabatrin; -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 ∼1–2 pmol/30 µl/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 ∼6–8 pmol/30 µl/30-min sample). Both inhibitors gave similar results. Depolarisation with 100 mM K+ gave large increases in GABA release in control (∼20–60 pmol/30 µl/30-min sample) and treated animals. The 8- and 21-day-treated animals showed significant increases in the stimulated release compared with control animals (∼80–100 pmol/30 µl/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.

Item Type:Article
Uncontrolled Keywords:GABA;GABA transaminase;Ethanolamine O-sulphate;-Vinyl-GABA;Hippocampus;Intracerebral dialysis
Departments, units and centres:Department of Pharmacology > Department of Pharmacology
ID Code:3135
Journal or Publication Title:Journal of Neurochemistry
Deposited By:Library Staff
Deposited On:03 May 2012 11:09
Last Modified:03 May 2012 11:09

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