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Research ArticleArticle

Dependence of Nicotinic Acetylcholine Receptor Recovery from Desensitization on the Duration of Agonist Exposure

Raven Reitstetter, Ronald J. Lukas and Raphael Gruener
Journal of Pharmacology and Experimental Therapeutics May 1999, 289 (2) 656-660;
Raven Reitstetter
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Ronald J. Lukas
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Raphael Gruener
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Abstract

When subjected to prolonged exposure to nicotinic agonists, nicotinic acetylcholine receptors undergo desensitization, resulting in an inactive receptor that does not allow for the passage of ions. The induction of desensitization of diverse nicotinic acetylcholine receptor subtypes in muscle, ganglia, or brain is likely to play important modulatory roles in synaptic transmission. Furthermore, nicotinic receptor desensitization may contribute to behavioral changes in humans or animals subjected to prolonged nicotine exposure pharmacologically or through the use of tobacco products. We investigated the recovery from desensitization of muscle-type nicotinic acetylcholine receptors in TE671/RD cells induced by exposure to acetylcholine or nicotine. Rates of recovery from desensitization are dependent on the length of agonist exposure and on the agonist used to induce desensitization. Increasing the time of exposure results in an increase in the time constant of recovery for both agonists. The recovery from nicotine-induced desensitization is consistently faster than the recovery from acetylcholine-induced desensitization regardless of whether nicotine or acetylcholine is used to assess levels of desensitization. These findings suggest the existence of more than one state of receptor desensitization and that nicotinic agonists vary in their efficiency of inducing receptors to states of differing depths of desensitization.

Footnotes

  • Send reprint requests to: Dr. Raphael Gruener, Department of Physiology, College of Medicine, University of Arizona, P.O. Box 245051, Tucson, AZ 85724-5051. E-mail rgruener{at}u.arizona.edu

  • ↵1 This study was funded by Arizona Disease Control Research Commission Grant 9730.

  • ↵2 Present address: Barrow Neurological Institute, Phoenix, AZ 85013.

  • Abbreviations:
    nAChR
    nicotinic acetylcholine receptor
    ACh
    acetylcholine
    • Received August 12, 1998.
    • Accepted December 14, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 289 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 289, Issue 2
1 May 1999
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Research ArticleArticle

Dependence of Nicotinic Acetylcholine Receptor Recovery from Desensitization on the Duration of Agonist Exposure

Raven Reitstetter, Ronald J. Lukas and Raphael Gruener
Journal of Pharmacology and Experimental Therapeutics May 1, 1999, 289 (2) 656-660;

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Research ArticleArticle

Dependence of Nicotinic Acetylcholine Receptor Recovery from Desensitization on the Duration of Agonist Exposure

Raven Reitstetter, Ronald J. Lukas and Raphael Gruener
Journal of Pharmacology and Experimental Therapeutics May 1, 1999, 289 (2) 656-660;
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