title: Characterization of specific succinate binding site in brain synaptic membranes.
abstract: A synaptic receptor for gamma-hydroxybutyric acid (GHB) --a naturally occurring metabolite of succinic acid--interacting succinate has been disclosed in rat and human nucleus accumbens (NA) subcellular fractions, but the molecular properties of this recognition site were not characterised. To address the presumed recognition site for succinate, the pharmacological profile of [3H]succinate binding to synaptic membranes prepared from rat forebrain and human NA samples has been investigated. Specific [3H]succinate binding sites in the human NA synaptic membrane fraction showed a strong pH-dependence and were characterized by binding of succinate (IC50 succinate=2.9+/-0.6 microM), GHB (IC50 GHB=2.1 +/-1.3 microM) and gap junction blocker carbenoxolone (IC50 = 7.1 +/-5.8 microM). A similar [3H]succinate binding profile was found in rat forebrain synaptic membrane fractions. We conclude the existence of a pHo-dependent synaptic membrane binding site for the intermediary metabolite succinate. The pharmacological properties of this recognition site may possibly suggest the existence of a hemichannel-like target protein for succinate.
authors: Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest. tmolnar@chemres.hu
authors: Tünde
authors: T
authors: Molnár
authors: Erzsébet Kutiné
authors: EK
authors: Fekete
authors: Julianna
authors: J
authors: Kardos
authors: Miklós
authors: M
authors: Palkovits
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002102:Cadaver; D002229:Carbenoxolone / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006885:Hydroxybutyrates / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D019802:Succinic Acid / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism*; D014316:Tritium
chemical_list: D006885:Hydroxybutyrates; D014316:Tritium; C111420:4-hydroxybutyric acid; D019802:Succinic Acid; D002229:Carbenoxolone