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Title: Relationship between muscarinic receptor occupancy and adenylate cyclase inhibition in the rabbit myocardium

Abstract

The muscarinic receptor-binding properties of a series of muscarinic drugs were compared with their effects on adenylate cyclase in membranes of the rabbit myocardium. When measured by competitive inhibition of (TH)-N-methylscopolamine binding, the competition curves of the various agonists were adequately described by the ternary complex model. This model assumes that the receptor can bind reversibly with a guanine nucleotide binding protein in the membrane and that the affinity of the agonist for the receptor-guanine nucleotide-binding protein complex is higher than that for the free receptor. A satisfactory fit of the ternary complex model to the data could only be achieved assuming that very little receptor is precoupled with the guanine nucleotide-binding protein in the absence of agonist. There was good agreement between the efficacy of each agonist as measured by inhibition of adenylate cyclase and the estimate of the positive cooperativity between the binding of the agonist receptor complex and the guanine nucleotide-binding protein. Guanosine 5'-triphosphate (0.1 mM) had no significant effect on the binding of (TH)N-methylscopolamine but caused an increase in the concentration of the various agonists required for half-maximal receptor occupancy. There was good correlation between efficacy as measured by inhibition of adenylate cyclase and the influencemore » of guanosine 5'-triphosphate on binding properties.« less

Authors:
Publication Date:
Research Org.:
Univ. of California School of Medicine, Los Angeles
OSTI Identifier:
6296747
Resource Type:
Journal Article
Journal Name:
Mol. Pharmacol.; (United States)
Additional Journal Information:
Journal Volume: 5
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 59 BASIC BIOLOGICAL SCIENCES; AMINES; RADIORECEPTOR ASSAY; ENZYMES; INHIBITION; GUANOSINE; IN VITRO; MYOCARDIUM; RABBITS; RECEPTORS; TRITIUM COMPOUNDS; ANIMALS; AROMATICS; AZAARENES; BODY; CARDIOVASCULAR SYSTEM; HEART; HETEROCYCLIC COMPOUNDS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MAMMALS; MUSCLES; NUCLEOSIDES; NUCLEOTIDES; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PURINES; RIBOSIDES; TRACER TECHNIQUES; VERTEBRATES; 550601* - Medicine- Unsealed Radionuclides in Diagnostics; 550201 - Biochemistry- Tracer Techniques

Citation Formats

Ehlert, F J. Relationship between muscarinic receptor occupancy and adenylate cyclase inhibition in the rabbit myocardium. United States: N. p., 1985. Web.
Ehlert, F J. Relationship between muscarinic receptor occupancy and adenylate cyclase inhibition in the rabbit myocardium. United States.
Ehlert, F J. 1985. "Relationship between muscarinic receptor occupancy and adenylate cyclase inhibition in the rabbit myocardium". United States.
@article{osti_6296747,
title = {Relationship between muscarinic receptor occupancy and adenylate cyclase inhibition in the rabbit myocardium},
author = {Ehlert, F J},
abstractNote = {The muscarinic receptor-binding properties of a series of muscarinic drugs were compared with their effects on adenylate cyclase in membranes of the rabbit myocardium. When measured by competitive inhibition of (TH)-N-methylscopolamine binding, the competition curves of the various agonists were adequately described by the ternary complex model. This model assumes that the receptor can bind reversibly with a guanine nucleotide binding protein in the membrane and that the affinity of the agonist for the receptor-guanine nucleotide-binding protein complex is higher than that for the free receptor. A satisfactory fit of the ternary complex model to the data could only be achieved assuming that very little receptor is precoupled with the guanine nucleotide-binding protein in the absence of agonist. There was good agreement between the efficacy of each agonist as measured by inhibition of adenylate cyclase and the estimate of the positive cooperativity between the binding of the agonist receptor complex and the guanine nucleotide-binding protein. Guanosine 5'-triphosphate (0.1 mM) had no significant effect on the binding of (TH)N-methylscopolamine but caused an increase in the concentration of the various agonists required for half-maximal receptor occupancy. There was good correlation between efficacy as measured by inhibition of adenylate cyclase and the influence of guanosine 5'-triphosphate on binding properties.},
doi = {},
url = {https://www.osti.gov/biblio/6296747}, journal = {Mol. Pharmacol.; (United States)},
number = ,
volume = 5,
place = {United States},
year = {Fri Nov 01 00:00:00 EST 1985},
month = {Fri Nov 01 00:00:00 EST 1985}
}