Abstract
γ-Hydroxybutyrate (GHB) has been reported to be a ligand for GABAB receptor(s), although with low or very low affinity (IC50 = 150–796 μM). In addition, several reports argue for a role of GHB via GABAB receptors in bothin vivo and in vitro electrophysiological experiments. In the present study, we demonstrate that the inhibition of GHB’s conversion into GABA by rat brain membranes blocks the ability of GHB to interfere with GABAB binding. In particular, the inhibition of GHB dehydrogenase by valproate or ethosuximide and the blockade of GABA-T by aminooxyacetic acid induce the disappearance of the GABA-like effect of GHB at GABAB, but also at GABAA, receptors. This finding could explain the misinterpretation of in vit́ro or in vivo experiments where GHB possesses a GABA-like effect. But in addition, it is postulated that the normal metabolism of GHB in brain induces GABAB mechanisms that could be blocked by the administration of valproate or ethosuximide.
Footnotes
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Send reprint requests to: Michel Maitre, L.N.M.I.C, Centre de Neurochimie, 5, rue Blaise Pascal, 67084 Strasbourg Cedex, France.
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↵1 This work was supported by a grant from DRET 93-172.
- Abbreviations:
- GHB
- γ-hydroxybutyrate
- SSA
- succinic semialdehyde
- GABA-T
- γ-aminobutyrate transaminase
- Received September 3, 1996.
- Accepted January 30, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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