Muscarinic M3 receptors mediate contractions in rabbit, endothelium-denuded aorta in vitro.
1. Muscarinic receptors mediating contraction of rabbit endothelium-denuded aorta have been characterized functionally, in vitro, using a range of antagonists (atropine, pirenzepine, methoctramine, himbacine, 4-diphenyl-acetoxy-N-methyl piperidine methiodide (4-DAMP) and para-fluoro-hexahydro-siladifenidol (p-F-HHSiD). 2. The non-selective muscarinic agonist, (+)cis-dioxolane, induced concentration-dependent contractions of endothelium-denuded aortic rings. The potency (EC50) of (+)cis-dioxolane was 1.0 +/- 0.4 microM and the maximal increase in isometric tension was 944 +/- 98 mg (mean +/- SEM, n = 25). The concentration-effect curves to (+)cis-dioxolane were shifted to the right in the presence of antagonists, in a concentration-dependent manner. The following affinities (-log KB) were calculated; atropine, 9.4; pirenzepine, 6.6; methoctramine, 5.9; himbacine, 7.1; 4-DAMP, 9.2; and p-F-HHSiD, 7.7. 3. It is concluded that muscarinic M3 receptors mediate contractions of endothelium-denuded aorta. The low potency of (+)cis-dioxolane, when compared to its potency in other M3 receptor assays, suggests that the efficiency of receptor coupling, associated with contraction of this tissue, is poor.
Watson
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Institute of Pharmacology, Palo Alto, CA 94304.
Eglen
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D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D004148:Dioxolanes / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000502:physiology*; D014661:Vasoconstriction
D004148:Dioxolanes; D010880:Piperidines; D011976:Receptors, Muscarinic; C024310:2-methyldioxolane; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium