![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Molecular Pharmacology, Vol 6, 357-382, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics
1 University Department of Pharmacology, South Parks Road, Oxford, England
Evidence is presented that desensitization to cholinergic agonists in chick and leech muscle is a process involving receptor inactivation. Various possible mechanisms that could account for slow inactivation of receptors by agonists were analyzed mathematically, and expressions were obtained for the rate and extent of desensitization expected under various conditions.
With the majority of agonists tested there appeared to be the same relationship between the response and the amount of desensitization produced. Certain agonists, however, were relatively more effective in causing desensitization.
The kinetics of development of and recovery from desensitization were studied in chick and frog muscle. Reactivation of desensitized receptors occurred exponentially. In chick muscle the rate constant for recovery was the same (0.3 min-1) regardless of what agonist had been used to produce the desensitization.
In chick muscle, tubocurarine decreased pari passu the response and the desensitization produced by carbachol or suxamethonium. Tubocurarine increased the desensitization produced by the partial agonist n-decyltrimethylammonium.
These results are compatible with the cyclic model for desensitization suggested by Katz and Thesleff [J. Physiol. (London) 138, 63 (1957)], with the additional factor that certain drugs may have a preferential affinity for desensitized, compared with normal, receptors. The process of receptor activation may be very closely related to the transition from normal to desensitized receptors brought about by agonist drugs.
Note:
ACKNOWLEDGMENTS
We are grateful to Dr. E. W. Gill and Dr. R. B.
Barlow for their generosity in supplying many of
the compounds used.
This article has been cited by other articles:
|
|
 |
|
  E. Sokolova, A. Skorinkin, I. Moiseev, A. Agrachev, A. Nistri, and R. Giniatullin Experimental and Modeling Studies of Desensitization of P2X3 Receptors Mol. Pharmacol., July 1, 2006; 70(1): 373 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Pratt, T. S. Brink, P. Bergson, M. M. Voigt, and S. P. Cook Use-Dependent Inhibition of P2X3 Receptors by Nanomolar Agonist J. Neurosci., August 10, 2005; 25(32): 7359 - 7365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Dahan, M. I. Dibas, E. J. Petersson, V. C. Auyeung, B. Chanda, F. Bezanilla, D. A. Dougherty, and H. A. Lester A fluorophore attached to nicotinic acetylcholine receptor {beta}M2 detects productive binding of agonist to the {alpha}{delta} site PNAS, July 6, 2004; 101(27): 10195 - 10200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chang, E. Ghansah, Y. Chen, J. Ye, and D. S. Weiss Desensitization Mechanism of GABA Receptors Revealed by Single Oocyte Binding and Receptor Function J. Neurosci., September 15, 2002; 22(18): 7982 - 7990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Eldefrawi, A. G. Britten, and A. T. Eldefrawi Acetylcholine Binding to Torpedo Electroplax: Relationship to Acetylcholine Receptors Science, July 23, 1971; 173(3994): 338 - 340. [Abstract] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
