Gamma-hydroxybutyric acid binding sites in rat and human brain synaptosomal membranes.
The binding of gamma-hydroxy[2,3-3H]butyric acid (GHB) was characterized in rat and human brain synaptosomal membranes. Binding was shown to be saturable, pH dependent, and linear with protein concentration. There was a distinct regional distribution of binding sites in both rat and human brain, with the hippocampus being the richest and the cerebellum the poorest, in density of [3H]GHB binding sites. Competition and saturation experiments revealed two different population of binding sites, a high-affinity site with a KD1 of 580 nM and a B max1 of 1.8 pmoles/mg protein and a low-affinity site with a KD2 of 2.3 microM and a B max2 of 11.3 pmoles/mg protein. [3H]GHB binding was not inhibited by gamma-aminobutyric acid (GABA), GABA receptor agonists, opiate antagonists or anticonvulsant drugs. These data suggest that GHB may play a role as a neurotransmitter or neuromodulator in brain independent of GABA.
D000328:Adult; D000368:Aged; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D006801:Humans; D006885:Hydroxybutyrates / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D011963:Receptors, GABA-A; D012978:Sodium Oxybate / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
D000927:Anticonvulsants; D006885:Hydroxybutyrates; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D012978:Sodium Oxybate