gamma-Hydroxybutyrate conversion into GABA induces displacement of GABAB binding that is blocked by valproate and ethosuximide
Hechler, V.; Ratomponirina, C.; Maitre, M.
Journal of Pharmacology and Experimental Therapeutics 281(2): 753-760
1997
ISSN/ISBN: 0022-3565 PMID: 9152382 Document Number: 481498
gamma-Hydroxybutyrate (GHB) has been reported to be a ligand for GABA-B receptor(s), although with low or very low affinity (IC-50 = 150-796 mu-M). In addition, several reports argue for a role of GHB via GABA-B receptors in both in 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 GABA-B 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 GABA-B, but also at GABA-A, receptors. This finding could explain the misinterpretation of in vitro 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 GABA-B mechanisms that could be blocked by the administration of valproate or ethosuximide.