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 b ladder were studied with the use of muscarinic agonists and antagonist s. 2 McN-A-343 induced only weak contractile responses of the bladder muscle. In contrast, oxotremorine showed higher potency than either ac etylcholine or bethanechol in inducing a contractile response (the res pective pot values were 6.38 +/- 0.25, 4.82 +/- 0.24 and 4.42 +/- 0.14 ). 3 The M-2 antagonists, methoctramine (10(-9) M to 10(-5) M) and gal lamine (10(-9) M to 10(-5) M), did not reduce acetylcholine-induced (1 0(-5) M) contractions of the bladder muscle strip. On the other hand, 4-diphenyl-acetoxy-N-methyl piperidine methiodide (4-DAMP, 10(-10) M t o 10(-7) M), an M-3 receptor blocker, effectively antagonized the acet ylcholine-induced contractions in a concentration-dependent manner. 4- DAMP had a similar pA(2) value to those of the non-selective antagonis ts, atropine and scopolamine (pA(2) values were 8.26 +/- 0.05, 8.36 +/ - 0.05 and 8.41 +/- 0.11, respectively). Pirenzepine, an MI blocker, a ntagonized the contractions at higher concentrations (10(-8) M to 10(- 5) M, pA(2) = 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 M-3; and (2) the muscarinic agonist oxot remorine was more potent than acetylcholine and bethanechol in inducin g a contractile response.