Lack of specificity in cation effects on solubilized benzodiazepine receptor.
Receptors for benzodiazepines (BZ) and beta-carboline-carboxylic acid ethyl ester (beta-CCE) has been solubilized with decanoly-N-methylglucamide (DMG), a new kind of nonionic detergent. The apparent dissociation constants of diazepam and beta-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 [3H]beta-CCE essentially parallels that of [3H]diazepam and that both sedimentation coefficients were 10.5S. Co2+ and Ni2+, which increase [3H]diazepam binding and decrease [3H]beta-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 [3H]diazepam and [3H]beta-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 with DMG.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology*; D002499:Centrifugation, Density Gradient; D003035:Cobalt / Q000494:pharmacology; D003902:Detergents; D003975:Diazepam / Q000494:pharmacology; D005227:Fatty Acids; D005944:Glucosamine / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009532:Nickel / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000302:isolation & purification; D013570:Synaptic Membranes / Q000378:metabolism
D002243:Carbolines; D002413:Cations, Divalent; D003902:Detergents; D005227:Fatty Acids; D011963:Receptors, GABA-A; D003035:Cobalt; C024915:beta-carboline-3-carboxylic acid ethyl ester; D009532:Nickel; C042221:decanoyl-N-methylglucamide; D008274:Magnesium; D005944:Glucosamine; D003975:Diazepam; D002118:Calcium