Abstract
We report that preapplication of ivermectin, in the micromolar range, strongly enhances the subsequent acetylcholine-evoked current of the neuronal chick or human α7 nicotinic acetylcholine receptors reconstituted in Xenopus laevis oocytes and K-28 cells. This potentiation does not result from nonspecific Cl−currents. The concomitant increase in apparent affinity and cooperativity of the dose-response curve suggest that ivermectin acts as a positive allosteric effector. This interpretation is supported by the observation of an increase in efficiency of a partial agonist associated with the potentiation and by the differential effect of ivermectin on mutants within the M2 channel domain. Ivermectin effects reveal a novel allosteric site for pharmacological agents on neuronal α7 nicotinic acetylcholine receptors.
Footnotes
- Received June 26, 1997.
- Accepted October 14, 1997.
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Send reprint requests to: D. Bertrand, Department of Physiology, University Medical Center, 1211 Geneva 4, Switzerland. E-mail: bertrand{at}cmu.unige.ch
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↵1 Current affiliation: Centre National de la Recherche Scientifique, 67400 Illkirch, France.
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This work was supported by the Swiss National Foundation and the Office Fédéral de l’Education et des Sciences (D.B.) and Collège de France, Association Française contre la Myopathie, Institut de la Santé et de la Recherche Médicale, Direction de la Recherche Etudes et Techniques, and Commission of the European Communities (Biotech, Biomed) (J.P.C.).
- The American Society for Pharmacology and Experimental Therapeutics
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