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 pot values were 6.38 ± 0.25, 4.82 ± 0.24 and 4.42 ± 0.14). 3. The M2 antagonists, methoctramine (10-9 M to 10-5 M) and gallamine (10-9 M to 10-5 M), did not reduce acetylcholine-induced (10-5 M) contractions of the bladder muscle strip. On the other hand, 4-diphenyl-acetoxy-N-methyl piperidine methiodide (4-DAMP, 10-10 M to 10-7 M), 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 (10-8 M to 10-5 M, 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.
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