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Title: Regional distribution of M1, M2 and non-M1, non-M2 subtypes of muscarinic binding sites in rat brain

Abstract

The distribution of subtypes of the muscarinic receptor in homogenates of the rat brain was investigated by measuring the competitive inhibition of the binding (3H)N-methylscopolamine by pirenzepine and AF-DX 116 (11((2-((diethylamino)methyl)-1-piperidinyl)acetyl)-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one). In most brain regions, the competitive binding curves for AF-DX 116 and pirenzepine were consistent with a two-site model. The dissociation constant of pirenzepine for its high-affinity site (M1 receptor) was approximately 10(-8) M, whereas the dissociation constant of AF-DX 116 for its high affinity site (M2 receptor) was approximately 10(-7) M. In many regions, particularly those in the forebrain, the sum of the densities of the M1 and M2 binding sites was substantially less than 100% of the total sites, indicating the existence of a third population of sites lacking high affinity for both pirenzepine and AF-DX 116. We have designated these latter sites as non-M1, non-M2 muscarinic receptors. In general, the densities of the M1 and non-M1, non-M2 binding sites were highest in cerebral cortex, corpus striatum and hippocampus, intermediate in thalamus and hypothalamus, and lowest in midbrain, medulla-pons and cerebellum, whereas the M2 binding site had a relatively low, uniform density throughout the brain. The binding capacity of (3H)N-methylquinuclidinyl benzilate was estimated to be 20more » to 30% lower than that of (3H)quinuclidinyl benzilate in various regions of the forebrain, but not in more caudal regions of the brain where the two radioligands had approximately the same binding capacities.« less

Authors:
;  [1]
  1. Univ. of California, Irvine (USA)
Publication Date:
OSTI Identifier:
6215028
Resource Type:
Journal Article
Journal Name:
Journal of Pharmacology and Experimental Therapeutics; (USA)
Additional Journal Information:
Journal Volume: 255:3; Journal ID: ISSN 0022-3565
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; PARASYMPATHOMIMETICS; RECEPTORS; TISSUE DISTRIBUTION; AFFINITY; BIOCHEMICAL REACTION KINETICS; BRAIN; CPB; INHIBITION; MATHEMATICAL MODELS; PARASYMPATHOLYTICS; RATS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; CENTRAL NERVOUS SYSTEM; DISTRIBUTION; DRUGS; HYDROGEN COMPOUNDS; ISOTOPE APPLICATIONS; KINETICS; MAMMALS; MEMBRANE PROTEINS; NERVOUS SYSTEM; ORGANIC COMPOUNDS; ORGANS; PROTEINS; REACTION KINETICS; RODENTS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Ehlert, F J, and Tran, L P. Regional distribution of M1, M2 and non-M1, non-M2 subtypes of muscarinic binding sites in rat brain. United States: N. p., 1990. Web.
Ehlert, F J, & Tran, L P. Regional distribution of M1, M2 and non-M1, non-M2 subtypes of muscarinic binding sites in rat brain. United States.
Ehlert, F J, and Tran, L P. 1990. "Regional distribution of M1, M2 and non-M1, non-M2 subtypes of muscarinic binding sites in rat brain". United States.
@article{osti_6215028,
title = {Regional distribution of M1, M2 and non-M1, non-M2 subtypes of muscarinic binding sites in rat brain},
author = {Ehlert, F J and Tran, L P},
abstractNote = {The distribution of subtypes of the muscarinic receptor in homogenates of the rat brain was investigated by measuring the competitive inhibition of the binding (3H)N-methylscopolamine by pirenzepine and AF-DX 116 (11((2-((diethylamino)methyl)-1-piperidinyl)acetyl)-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one). In most brain regions, the competitive binding curves for AF-DX 116 and pirenzepine were consistent with a two-site model. The dissociation constant of pirenzepine for its high-affinity site (M1 receptor) was approximately 10(-8) M, whereas the dissociation constant of AF-DX 116 for its high affinity site (M2 receptor) was approximately 10(-7) M. In many regions, particularly those in the forebrain, the sum of the densities of the M1 and M2 binding sites was substantially less than 100% of the total sites, indicating the existence of a third population of sites lacking high affinity for both pirenzepine and AF-DX 116. We have designated these latter sites as non-M1, non-M2 muscarinic receptors. In general, the densities of the M1 and non-M1, non-M2 binding sites were highest in cerebral cortex, corpus striatum and hippocampus, intermediate in thalamus and hypothalamus, and lowest in midbrain, medulla-pons and cerebellum, whereas the M2 binding site had a relatively low, uniform density throughout the brain. The binding capacity of (3H)N-methylquinuclidinyl benzilate was estimated to be 20 to 30% lower than that of (3H)quinuclidinyl benzilate in various regions of the forebrain, but not in more caudal regions of the brain where the two radioligands had approximately the same binding capacities.},
doi = {},
url = {https://www.osti.gov/biblio/6215028}, journal = {Journal of Pharmacology and Experimental Therapeutics; (USA)},
issn = {0022-3565},
number = ,
volume = 255:3,
place = {United States},
year = {Sat Dec 01 00:00:00 EST 1990},
month = {Sat Dec 01 00:00:00 EST 1990}
}