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Title: Rate constants of agonist binding to muscarinic receptors in rat brain medulla. Evaluation by competition kinetics

The method of competition kinetics, which measures the binding kinetics of an unlabeled ligand through its effect on the binding kinetics of a labeled ligand, was employed to investigate the kinetics of muscarinic agonist binding to rat brain medulla pons homogenates. The agonists studied were acetylcholine, carbamylcholine, and oxotremorine, with N-methyl-4-(TH)piperidyl benzilate employed as the radiolabeled ligand. Our results suggested that the binding of muscarinic agonists to the high affinity sites is characterized by dissociation rate constants higher by 2 orders of magnitude than those of antagonists, with rather similar association rate constants. Our findings also suggest that isomerization of the muscarinic receptors following ligand binding is significant in the case of antagonists, but not of agonists. Moreover, it is demonstrated that in the medulla pons preparation, agonist-induced interconversion between high and low affinity bindings sites does not occur to an appreciable extent.
Authors:
; ;
Publication Date:
OSTI Identifier:
6334485
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Biol. Chem.; (United States); Journal Volume: 15
Research Org:
Tel Aviv Univ., Israel
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; PARASYMPATHOMIMETICS; RADIORECEPTOR ASSAY; ACETYLCHOLINE; BIOCHEMICAL REACTION KINETICS; BRAIN; CHOLINE; HOMOGENATES; IN VITRO; PIPERIDINES; RATS; RECEPTORS; TRITIUM COMPOUNDS; ALCOHOLS; AMINES; AMMONIUM COMPOUNDS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; AZINES; BODY; CENTRAL NERVOUS SYSTEM; DRUGS; ESTERS; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; ISOTOPE APPLICATIONS; KINETICS; LABELLED COMPOUNDS; LIPOTROPIC FACTORS; MAMMALS; NERVOUS SYSTEM; NEUROREGULATORS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PYRIDINES; QUATERNARY COMPOUNDS; REACTION KINETICS; RODENTS; TRACER TECHNIQUES; VERTEBRATES 550601* -- Medicine-- Unsealed Radionuclides in Diagnostics