Allosteric interactions between the membrane-bound acetylcholine receptor and chemical mediators: equilibrium measurements.
An approach to equilibrium dialysis measurements has been developed which enables one to study the interaction of chemical mediators with the membrane-bound acetylcholine receptor and to gain information of a type previously obtainable only with soluble proteins. Equilibrium dialysis experiments conducted at pH 7.0,4 degrees C, and mu = 0.18 M, with electroplax membrane preparations from Electrophorus electricus revealed apparently homogeneous binding isotherms for decamethonium with dissociation constants in the range of 0.2-0.4 muM. The following new information has been obtained. (1) The activators of neural transmission, decamethonium and carbamylcholine, occupy overlapping binding sites. (2) These activators and the inhibitors, alpha-bungarotoxin and d-tubocurarine, compete for only one-half of the sites available to them even through the stoichiometry of these is 1:1 as measured with decamethonium (a reversibly binding activator) and alpha-bungarotoxin (an irreversible specific inhibitor). Different receptor molecules, preexisting nonequivalent binding sites, or an allosteric mechanism involving ligand-induced conformational changes are often considered to account for such observations.
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D001667:Binding, Competitive; D002038:Bungarotoxins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003650:Decamethonium Compounds / Q000494:pharmacology; D004557:Electric Organ / Q000378:metabolism*; D004593:Electrophorus; D007700:Kinetics; D011950:Receptors, Cholinergic / Q000378:metabolism; D012910:Snake Venoms / Q000378:metabolism
D002038:Bungarotoxins; D003650:Decamethonium Compounds; D011950:Receptors, Cholinergic; D012910:Snake Venoms; D000110:Acetylcholinesterase; D000109:Acetylcholine