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Muscarinic acetylcholine receptors : investigation of interactions with agonists and antagonists
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- Hedlund, Britta, 1955- (författare)
- Stockholms universitet
- (creator_code:org_t)
- ISBN 917146168X
- Stockholm : Stockholm University, 1981
- Engelska 59 s.
- Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
Abstract
Ämnesord
Stäng
- In the present investigation interactions of agonists and antagonists with the muscarinic acetylcholine receptor from rat cerebral cortex and rat ileum smooth muscle have been characterized.It is suggested that the binding of antagonist involves two sequential equilibria, an association reaction followed by isomerization of the receptor-antagonist complex. The rate constants for these steps are dependent on the antagonist used, as well as on the reaction conditions. Muscarinic receptors are present in at least two different conformational states on the membrane, as demonstrated by the agonist binding experiments, and the receptor protein is able to bind at least two ligand molecules (agonists and/or antagonists) simultaneously. Studies with 3H-pilocarpine indicate that at least two, and probably more, agonist molecules can be bound to the receptor simultaneously. The conformation which binds agonist with high affinity seems to be sensitive to changes in the membrane potential or in the open/closed state of a coupled Na+-channel. This conclusion is supported by the effects of drugs acting on the Na+-channel and of depolarizing agents on ligand binding to the muscarinic receptor. The conformation with high affinity for the agonist and the low affinity conformer mediate different ion -fluxes across the membrane, respectively.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
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