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.
M Qume, P S Whitton, L J Fowler
文献索引:J. Neurochem. 64 , 2256, (1995)
全文:HTML全文
摘要
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; 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.
相关化合物
相关文献:
2010-01-01
[Chem. Res. Toxicol. 23 , 171-83, (2010)]
2011-12-01
[J. Sci. Ind. Res. 65(10) , 808, (2006)]
2007-05-01
[Nat. Chem. Biol. 3(5) , 268-273, (2007)]
2010-03-01
[Eur. J. Med. Chem. 45 , 930-40, (2010)]
2010-12-15
[Bioorg. Med. Chem. Lett. 20 , 7312-6, (2010)]