Muscarinic receptor binding in rat brain using the agonist, [3H]cis methyldioxolane

Frederick J. Ehlert, Yvon Dumont, William R. Roeske, Henry I. Yamamura

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Muscarinic receptor binding was measured in rat forebrain preparations using the muscarinic agonist, [3H]cis methyldioxolane ([3H]CD). The results of equilibrium binding studies using [3H]CD concentrations between 0.5-64 nM showed that [3H]CD binding did not saturate in this concentration range, although the binding isotherm was concave downward. Nonlinear regression analysis of the binding data revealed the presence of two populations of muscarinic receptors having dissociation constants of 1.83 and 123 nM and binding capacities of 85 and 1320 fmol/mg protein, respectively. Competitive inhibition experiments showed that [3H]CD binding was readily displaced by several muscarinic agonists and antagonists. The stereospecificity of [3H]CD binding was demonstrated in competitive inhibition experiments using the stereoisomers of benzetimide and acetyl-β-methylcholine. Dexetimide was 10,000 times more potent than levetimide and l-acetyl-β-methylcholine was 520 times more potent than d-acetyl-β-methylcholine. A variety of nonmuscarinic cholinergic drugs were not effective at inhibiting [3H]CD binding at a concentration of 10 μM.

Original languageEnglish (US)
Pages (from-to)961-967
Number of pages7
JournalLife Sciences
Volume26
Issue number12
DOIs
StatePublished - Mar 24 1980
Externally publishedYes

Fingerprint

Dexetimide
Muscarinic Receptors
Rats
Muscarinic Agonists
Brain
Stereoisomerism
Muscarinic Antagonists
Prosencephalon
Regression analysis
Cholinergic Agents
Isotherms
Experiments
Regression Analysis
Population
methylcholine
2-methyldioxolane
Proteins

ASJC Scopus subject areas

  • Pharmacology

Cite this

Muscarinic receptor binding in rat brain using the agonist, [3H]cis methyldioxolane. / Ehlert, Frederick J.; Dumont, Yvon; Roeske, William R.; Yamamura, Henry I.

In: Life Sciences, Vol. 26, No. 12, 24.03.1980, p. 961-967.

Research output: Contribution to journalArticle

Ehlert, Frederick J. ; Dumont, Yvon ; Roeske, William R. ; Yamamura, Henry I. / Muscarinic receptor binding in rat brain using the agonist, [3H]cis methyldioxolane. In: Life Sciences. 1980 ; Vol. 26, No. 12. pp. 961-967.
@article{0a2d6cc678c049a5afb736c0648bfec9,
title = "Muscarinic receptor binding in rat brain using the agonist, [3H]cis methyldioxolane",
abstract = "Muscarinic receptor binding was measured in rat forebrain preparations using the muscarinic agonist, [3H]cis methyldioxolane ([3H]CD). The results of equilibrium binding studies using [3H]CD concentrations between 0.5-64 nM showed that [3H]CD binding did not saturate in this concentration range, although the binding isotherm was concave downward. Nonlinear regression analysis of the binding data revealed the presence of two populations of muscarinic receptors having dissociation constants of 1.83 and 123 nM and binding capacities of 85 and 1320 fmol/mg protein, respectively. Competitive inhibition experiments showed that [3H]CD binding was readily displaced by several muscarinic agonists and antagonists. The stereospecificity of [3H]CD binding was demonstrated in competitive inhibition experiments using the stereoisomers of benzetimide and acetyl-β-methylcholine. Dexetimide was 10,000 times more potent than levetimide and l-acetyl-β-methylcholine was 520 times more potent than d-acetyl-β-methylcholine. A variety of nonmuscarinic cholinergic drugs were not effective at inhibiting [3H]CD binding at a concentration of 10 μM.",
author = "Ehlert, {Frederick J.} and Yvon Dumont and Roeske, {William R.} and Yamamura, {Henry I.}",
year = "1980",
month = "3",
day = "24",
doi = "10.1016/0024-3205(80)90117-4",
language = "English (US)",
volume = "26",
pages = "961--967",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "12",

}

TY - JOUR

T1 - Muscarinic receptor binding in rat brain using the agonist, [3H]cis methyldioxolane

AU - Ehlert, Frederick J.

AU - Dumont, Yvon

AU - Roeske, William R.

AU - Yamamura, Henry I.

PY - 1980/3/24

Y1 - 1980/3/24

N2 - Muscarinic receptor binding was measured in rat forebrain preparations using the muscarinic agonist, [3H]cis methyldioxolane ([3H]CD). The results of equilibrium binding studies using [3H]CD concentrations between 0.5-64 nM showed that [3H]CD binding did not saturate in this concentration range, although the binding isotherm was concave downward. Nonlinear regression analysis of the binding data revealed the presence of two populations of muscarinic receptors having dissociation constants of 1.83 and 123 nM and binding capacities of 85 and 1320 fmol/mg protein, respectively. Competitive inhibition experiments showed that [3H]CD binding was readily displaced by several muscarinic agonists and antagonists. The stereospecificity of [3H]CD binding was demonstrated in competitive inhibition experiments using the stereoisomers of benzetimide and acetyl-β-methylcholine. Dexetimide was 10,000 times more potent than levetimide and l-acetyl-β-methylcholine was 520 times more potent than d-acetyl-β-methylcholine. A variety of nonmuscarinic cholinergic drugs were not effective at inhibiting [3H]CD binding at a concentration of 10 μM.

AB - Muscarinic receptor binding was measured in rat forebrain preparations using the muscarinic agonist, [3H]cis methyldioxolane ([3H]CD). The results of equilibrium binding studies using [3H]CD concentrations between 0.5-64 nM showed that [3H]CD binding did not saturate in this concentration range, although the binding isotherm was concave downward. Nonlinear regression analysis of the binding data revealed the presence of two populations of muscarinic receptors having dissociation constants of 1.83 and 123 nM and binding capacities of 85 and 1320 fmol/mg protein, respectively. Competitive inhibition experiments showed that [3H]CD binding was readily displaced by several muscarinic agonists and antagonists. The stereospecificity of [3H]CD binding was demonstrated in competitive inhibition experiments using the stereoisomers of benzetimide and acetyl-β-methylcholine. Dexetimide was 10,000 times more potent than levetimide and l-acetyl-β-methylcholine was 520 times more potent than d-acetyl-β-methylcholine. A variety of nonmuscarinic cholinergic drugs were not effective at inhibiting [3H]CD binding at a concentration of 10 μM.

UR - http://www.scopus.com/inward/record.url?scp=0019331673&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019331673&partnerID=8YFLogxK

U2 - 10.1016/0024-3205(80)90117-4

DO - 10.1016/0024-3205(80)90117-4

M3 - Article

C2 - 7392777

AN - SCOPUS:0019331673

VL - 26

SP - 961

EP - 967

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 12

ER -