Characterization of specific succinate binding site in brain synaptic membranes.

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.