Molecular Pharmacology, Vol 20, 506-510, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Allosteric Effects of Volatile Anesthetics on the Membrane-Bound Acetylcholine Receptor Protein

II. Alteration of -Bungarotoxin Binding Kinetics

¹ Department of Biological Chemistry, School of Medicine, and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California 90024

The acetylcholine receptor (AcChR) protein isolated from Torpedo californica possesses two binding sites for -bungarotoxin. Although chemical modification and ligand-binding experiments have suggested that the two toxin binding sites are dissimilar, the toxin associates to its two sites on AcChR at identical rates. Incubation of AcChR-enriched membranes with volatile anesthetics and aliphatic alcohols retards the rate of association of toxin to one of its two binding sites on the high-affinity conformer of the protein. Kinetic plots of toxin binding characteristic of a single bimolecular association to AcChR become biphasic after incubation with these organic perturbants. Therefore, anesthetics and aliphatic alcohols alter the tertiary structure of the high-affinity conformer as well as stabilizing it relative to the low-affinity conformer. The differential response of the two toxin binding sites to these organic perturbants provides additional evidence of the non-equivalence of the binding loci.

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				J. Changeux, A Devillers-Thiery, and P Chemouilli Acetylcholine receptor: an allosteric protein Science, September 21, 1984; 225(4668): 1335 - 1345. [Abstract] [PDF]