Lack of specificity in cation effects on solubilized benzodiazepine receptor

摘要

Receptors for benzodiazepines (BZ) and β-carboline-carboxylic acid ethyl ester (β-CCE) has been solubilized with decanoly-N-methylglucamide (DMG), a new kind of nonionic detergent. The apparent dissociation constants of diazepam and β-CCE for solubilized receptor were similar to those for synaptic membranes. Sucrose density gradient centrifugation of the solubilized receptor protein revealed that the binding profile of 3Hβ-CCE essentially parallels that of 3Hdiazepam and that both sedimentation coefficients were 10.5S. Co2+and Ni2+, which increase 3Hdiazepam binding and decrease 3Hβ-CCE binding to synaptic membranes, remarkably increased the binding of both to the solubilized receptor. Mg2+and Ca2+, which had no effect on membrane receptor binding, also enhanced 3Hdiazepam and 3Hβ-CCE binding to the solubilized receptor. The increase in binding in the presence of these divalent cations was due to a change in the apparent number of binding sites, with no change in binding affinities. The relative lack of specificity in divalent cation effects on solubilized BZ receptor may be caused by separation or destruction of the cation recognition site or channel of the BZ receptor complex by solubilization of the synaptic membrane wit