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Title: Heterogeneity of binding of muscarinic receptor antagonists in rat brain homogenates

Abstract

The binding properties of (-)-(/sup 3/H)quinuclidinyl benzilate and (/sup 3/H) N-methylscopolamine to muscarinic acetylcholine receptors have been investigated in rat brain homogenates. The binding of both antagonists demonstrated high affinity and saturability. Analysis of the binding data resulted in linear Scatchard plots. However, (-)-(/sup 3/H)quinuclidinyl benzilate showed a significantly higher maximal binding capacity than that of (/sup 3/H)N-methylscopolamine. Displacement of both ligands with several muscarinic receptor antagonists resulted in competition curves in accordance with the law of mass-action for quinuclidinyl benzilate, atropine and scopolamine. A similar profile was found for the quaternary ammonium analogs of atropine and scopolamine when (/sup 3/H)N-methylscopolamine was used to label the receptors. However, when these hydrophilic antagonists were used to displace (-)-(/sup 3/H) quinuclidinyl benzilate binding, they showed interaction with high- and low-affinity binding sites. On the other hand, the nonclassical muscarinic receptor antagonist, pirenzepine, was able to displace both ligands from two binding sites. The present data are discussed in terms of the relationship of this anomalous heterogenity of binding of these hydrophilic muscarinic receptor antagonists and the proposed M1 and M2 receptor subtypes.

Authors:
;
Publication Date:
Research Org.:
Univ. of Maryland, Baltimore
OSTI Identifier:
5253914
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Pharmacol. Exp. Ther.; (United States); Journal Volume: 3
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ACETYLCHOLINE; RECEPTORS; PARASYMPATHOLYTICS; CHEMICAL BONDS; AFFINITY; AMINES; BENZILIC ACID; BRAIN; HOMOGENATES; IN VITRO; LIGANDS; RATS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; AMMONIUM COMPOUNDS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; CARBOXYLIC ACIDS; CENTRAL NERVOUS SYSTEM; DRUGS; ESTERS; HYDROXY ACIDS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MAMMALS; NERVOUS SYSTEM; NEUROREGULATORS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PARASYMPATHOMIMETICS; QUATERNARY COMPOUNDS; RODENTS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Lee, J.H., and el-Fakahany, E.E. Heterogeneity of binding of muscarinic receptor antagonists in rat brain homogenates. United States: N. p., 1985. Web.
Lee, J.H., & el-Fakahany, E.E. Heterogeneity of binding of muscarinic receptor antagonists in rat brain homogenates. United States.
Lee, J.H., and el-Fakahany, E.E. Sat . "Heterogeneity of binding of muscarinic receptor antagonists in rat brain homogenates". United States.
@article{osti_5253914,
title = {Heterogeneity of binding of muscarinic receptor antagonists in rat brain homogenates},
author = {Lee, J.H. and el-Fakahany, E.E.},
abstractNote = {The binding properties of (-)-(/sup 3/H)quinuclidinyl benzilate and (/sup 3/H) N-methylscopolamine to muscarinic acetylcholine receptors have been investigated in rat brain homogenates. The binding of both antagonists demonstrated high affinity and saturability. Analysis of the binding data resulted in linear Scatchard plots. However, (-)-(/sup 3/H)quinuclidinyl benzilate showed a significantly higher maximal binding capacity than that of (/sup 3/H)N-methylscopolamine. Displacement of both ligands with several muscarinic receptor antagonists resulted in competition curves in accordance with the law of mass-action for quinuclidinyl benzilate, atropine and scopolamine. A similar profile was found for the quaternary ammonium analogs of atropine and scopolamine when (/sup 3/H)N-methylscopolamine was used to label the receptors. However, when these hydrophilic antagonists were used to displace (-)-(/sup 3/H) quinuclidinyl benzilate binding, they showed interaction with high- and low-affinity binding sites. On the other hand, the nonclassical muscarinic receptor antagonist, pirenzepine, was able to displace both ligands from two binding sites. The present data are discussed in terms of the relationship of this anomalous heterogenity of binding of these hydrophilic muscarinic receptor antagonists and the proposed M1 and M2 receptor subtypes.},
doi = {},
journal = {J. Pharmacol. Exp. Ther.; (United States)},
number = ,
volume = 3,
place = {United States},
year = {Sat Jun 01 00:00:00 EDT 1985},
month = {Sat Jun 01 00:00:00 EDT 1985}
}