Advertisement

Ionic Effects on Antagonist Binding to the Muscarinic Receptor from Rat Cerebral Cortex

  • B. Hedlund
Part of the Advances in Behavioral Biology book series (ABBI, volume 25)

Abstract

Studies on the binding of the muscarinic antagonists 3H-N-methyl-4-piperidinyl benzilate (3H-4-NMPB) and 3H-3-quinuclidinyl benzilate (3H-3-QNB) have indicated deviations from first order kinetics of the association reaction under pseudofirst order conditions (8,9). Evidence has been provided for a mechanism of antagonist binding which involves two consecutive equilibria (6). Binding of both benzilates to the muscarinic receptor is followed by an isomerization of the receptor-antagonist complex:
$$ {\text{R}}{\mkern 1mu} {\text{ + }}{\mkern 1mu} {\text{A}}{\mkern 1mu} \mathop \rightleftharpoons \limits_{{{\text{k}}_{{\text{ - 1}}}}}^{{{\text{k}}_{\text{1}}}} {\mkern 1mu} {\text{AR}}{\mkern 1mu} \mathop \rightleftharpoons \limits_{{{\text{k}}_{{\text{ - 2}}}}}^{{{\text{k}}_{\text{2}}}} {\mkern 1mu} {\text{AR*}} $$
(1)
where R stands for receptor, A for antagonist, AR and AR* for the two different receptor-antagonist complexes and k1, k−1, k2 and k−2 are rate constants. This mechanism, involving an isomerization reaction, has been proposed for antagonist binding to receptors both in the central nervous system and in the periphery (6). Using 3H-4-NMPB further studies have been carried out for investigation of the ionic effects on the association and dissociation rates and on the equilibrium binding of the 3H-antagonist to the receptor.

Keywords

Muscarinic Receptor Dissociation Rate Ionic Effect Isomerization Reaction Equilibrium Binding 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Alberts, P. and Bartfai, T. (1976): J. Biol. Chem. 251:1543–1547.Google Scholar
  2. 2.
    Birdsall, N.J.M. and Hulme, E.C. (1976): J. Neurochem. 27:7–16.CrossRefGoogle Scholar
  3. 3.
    Bartfai, T., Study, R.E. and Greengard, P. (1977): IN Cholinergic Mechanisms and Psychopharmacology (ed) D.J. Jenden, Plenum Press, New York, pp. 285–295.Google Scholar
  4. 4.
    Hedlund, B. and Bartfai, T. (1979): Molec. Pharmacol. 15:531–544.Google Scholar
  5. 5.
    Hammer, R., Berrie, C.P., Birdsall, N.J.M., Burgen, A.S.V. and Hulme, E.C. (1980): Nature 283:90–92.CrossRefGoogle Scholar
  6. 6.
    Jarv, J., Hedlund, B. and Bartfai, T. (1979): J. Biol. Chem. 254:5595–5598.Google Scholar
  7. 7.
    Jarv, J., Hedlund, B. and Bartfai, T. (1980): J. Biol. Chem. 255:2649–2651.Google Scholar
  8. 8.
    Kloog, Y., Egozi, Y. and Sokolovsky, M. (1979): FEBS Lett. 97:265–268.CrossRefGoogle Scholar
  9. 9.
    Kloog, Y. and Sokolovsky, M. (1978): Brain Res. 144:31–48.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • B. Hedlund
    • 1
  1. 1.Department of Biochemistry, Arrhenius LaboratoryUniversity of StockholmStockholmSweden

Personalised recommendations