Ligand interactions with the acetylcholine receptor from Torpedo californica. Extensions of the allosteric model for cooperativity to half-of-site activity

Abstract

The solubilized acetylcholine (ACh) receptor from T. californica showed positive cooperativity in ACh binding with a dissociation constant of 1.2 .times. 10-8 M. Blockade of ACh binding by nicotine was competitive; blockade by d-tubocurarine appeared to result from an allosteric interaction that altered half of the ACh binding sites to a lower affinity form; decamethonium blockade displayed properties of competitive and allosteric inhibition suggesting less specificity for decamethonium binding than seen with either nicotine or d-tubocurarine inhibition data were evaluated by several possible models involving either differential competitive inhibition or allosteric inhibition. The data were best described by the allosteric model.