Abstract
The effects of edrophonium, eserine, decamethonium, d-tubocurarine, and gallamine on the kinetic parameters of membrane-bound and solubilized eel acetylcholinesterase were investigated. All assays were done using acetylcholine as substrate with a pH-stat in Ringer's solution. Edrophonium, an inhibitor of the anionic portion of the active site of acetylcholinesterase, was found to be a competitive inhibitor at a concentration of 0.1 µM and a mixed competitive-noncompetitive inhibitor at higher concentrations (1 and 10 µM) for both membrane-bound and solubilized acetylcholinesterase. Eserine (0.2-20 µM), a molecule which interacts with both the anionic and the esteratic portion of the active site of acetylcholinesterase, was a competitive inhibitor of the solubilized enzyme; inhibition by eserine of the membrane-bound enzyme was noncompetitive at 0.2 µM and mixed competitive-noncompetitive at higher concentrations of eserine (2 and 20 µM). The inhibition by decamethonium of both membrane-bound and solubilized acetylcholinesterase was noncompetitive at 3 and 100 µM decamethonium. d-Tubocurarine was found to affect the kinetics of both states of the enzyme in a mixed competitive-noncompetitive fashion. Gallamine, at concentrations as high as 100 µM, had no significant effect on either the Km or Vmax of membrane-bound or solubilized acetylcholinesterase. The effects of the membrane matrix on the interaction of these drugs with eel acetylcholinesterase are discussed.
ACKNOWLEDGMENTS We would like to thank Dr. J. Richardson and Ms. T. Bouchard for taking the electron micrographs, and Mr. H. P. Decker of Hoffmann-La Roche for a generous gift of edrophonium chloride.
- Copyright ©, 1975, by Academic Press, Inc.
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