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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Pharmacological characterization of the muscarinic receptor subtype mediating contraction of human peripheral airways.

The postjunctional muscarinic receptors mediating contraction of human bronchial smooth muscle have been characterized using four nonselective muscarinic receptor agonists and eight subtype selective and nonselective muscarinic antagonists. Carbachol, methacholine, oxotremorine M and (+)-cis-dioxolane all caused concentration-related contractions of human bronchial smooth muscle with a rank order of potency (pD2) of (+)-cis-dioxolane (7.3 +/- 0.2) > oxotremorine M (6.7 +/- 0.2) > carbachol (6.4 +/- 0.1) > methacholine (5.8 +/- 0.2, n = 5 for all). Maximum contractions were not significantly different between agonists, whether expressed as absolute my tension changes or as a percentage of the maximum response to 0.3 mM histamine. Antagonist apparent affinities (pKB) were determined against carbachol-induced contractions and the following rank order was obtained; 4-DAMP (9.4 +/- 0.3) > or = atropine (9.1 +/- 0.1) > zamifenacin (7.6 +/- 0.1) > hexahydrosiladifenidol (HHSiD; 7.1 +/- 0.1) > or = himbacine (7.0 +/- 0.3) > or = pirenzepine (6.8 +/- 0.2) > para-fluoro-hexahydrosiladifenidol (p-F-HHSiD; 6.7 +/- 0.1) > methoctramine (5.3 +/- 0.2). This rank order of antagonist affinities is consistent with activation of M3 receptors. The affinities of HHSiD, p-F-HHSiD and zamifenacin were, however, lower than those reported in guinea pig trachea.[1]


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