Pharmacologic comparison of selected agonists for the M1 muscarinic receptor in transfected murine fibroblast cells (B82)

L. Mei, J. Lai, H. I. Yamamura, W. R. Roeske

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Abstract

The radioligand binding and functional properties of 10 muscarinic agonists for the M1 muscarinic receptors were characterized on the murine fibroblast B82 cells, which have been transfected with the m1 gene. All of the muscarinic agonists completely inhibited [3H](-)methyl-3-quinuclidinyl benzilate binding to the M1 muscarinic receptor in the transfected B82 cells. Their apparent inhibition constant values for agonist/[3H](-)methyl-3-quinuclidinyl benzilate inhibition experiments correlate well with their EC50 values in stimulating phosphatidylinositide hydrolysis. Based on the maximal functional effects: (+)-cismethyl-dioxolane, oxotremorine-M, acetylcholine, carbachol and methacholine are most efficacious, McN-A-343 and arecoline are least efficacious, whereas the efficacies of oxotremorine and pilocarpine are intermediate. In addition, McN-A-343 inhibited carbachol-stimulated phosphatidylinositide hydrolysis. Spare receptors were detected for oxotremorine-M, methacholine and carbachol, but not the rest of the agonists, by comparing the receptor-occupancy curves with the concentration-response curves. These results suggest that the presence of a quaternary nitrogen (trimethylammonium group) within the structure of the agonist may be important for the expression of full agonist activity.

Original languageEnglish (US)
Pages (from-to)689-694
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume256
Issue number2
StatePublished - Jan 1 1991

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Muscarinic M1 Receptors
Carbachol
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride
Quinuclidinyl Benzilate
Muscarinic Agonists
Methacholine Chloride
Fibroblasts
Hydrolysis
Arecoline
Oxotremorine
Pilocarpine
Acetylcholine
Nitrogen
Genes
oxotremorine M

ASJC Scopus subject areas

  • Pharmacology

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Pharmacologic comparison of selected agonists for the M1 muscarinic receptor in transfected murine fibroblast cells (B82). / Mei, L.; Lai, J.; Yamamura, H. I.; Roeske, W. R.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 256, No. 2, 01.01.1991, p. 689-694.

Research output: Contribution to journalArticle

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