Pharmacological characterization of the muscarinic receptor subtypes responsible for the contractile response in the rat urinary bladder

1 Contractile responses of smooth muscle from the Wistar rat urinary bladder were studied with the use of muscarinic agonists and antagonists. 2 McN-A-343 induced only weak contractile responses of the bladder muscle. In contrast, oxotremorine showed higher potency than either acetylcholine or bethanechol in inducing a contractile response (the respective pD₂ values were 6.38 ± 0.25, 4.82 ± 0.24 and 4.42 ± 0.14). 3 The M₂ antagonists, methoctramine (10^?9m to 10^?5m ) and gallamine (10^?9m to 10^?5m ), did not reduce acetylcholine-induced (10^?5m ) contractions of the bladder muscle strip. On the other hand, 4-diphenyl-acetoxy-N-methyl piperidine methiodide (4-DAMP, 10^?10m to 10^?7m ), an M₃ receptor blocker, effectively antagonized the acetylcholine-induced contractions in a concentration-dependent manner. 4-DAMP had a similar pA₂ value to those of the non-selective antagonists, atropine and scopolamine (pA₂ values were 8.26 ± 0.05, 8.36 ± 0.05 and 8.41 ± 0.11, respectively). Pirenzepine, an M₁ blocker, antagonized the contractions at higher concentrations (10^?8m to 10^?5m , pA₂= 6.23 ± 0.04). 4 It is concluded that (1) the dominant muscarinic receptor subtype responsible for smooth muscle contraction in the rat urinary bladder is M₃; and (2) the muscarinic agonist oxotremorine was more potent than acetylcholine and bethanechol in inducing a contractile response.