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 μM 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 K_B) 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.