Muscarinic receptors in isolated urinary bladder smooth muscle from different mouse strains

1. The pharmacological characteristics of muscarinic receptors in male and female mouse urinary bladder smooth muscle from different strains (C57Bl/6, 129/SvJ and hybrid backcross N1F2) were studied. 2. (+)-Cis-dioxolane, oxotremorine-M, acetylcholine, carbachol and pilocarpine induced concentration-dependent contractions of the urinary bladder smooth muscle (range for pEC(50)=6.4-6.6, 6.2-6.7, 6.2-6.4, 5.4-6.0 and 0.0-5.1, T(max)=1.9-4.7 g, 1.3-3.4 g, 1.0-3.0 g, 1.4-2.4 and 0.0-0.3 g, respectively, n=4-6 depending on the gender and the strain). In females, these contractions were competitively antagonized by a range of muscarinic receptor antagonists (pK(B) value range, depending on the strain): atropine (8.0-8.9), pirenzepine (6.1-6.4), 4-DAMP (7.6-8.4), methoctramine (5.6-6.1), p-F-HHSiD (7.5-7.7), zamifenacin (7.7-8.4) and darifenacin (8.2-8.7). 3. In recontraction studies, in which the muscarinic M(3) receptor population was decreased, and conditions optimized to study M(2) receptor activation, methoctramine exhibited an affinity estimate consistent with muscarinic M(3) receptors (pK(B)=6.26+/-0.08, pA(2)=6.31+/-0.07; pK(B)=6.09+/-0.22, pA(2)=6.08+/-0.01 for female inbred strain 129/SvJ and hybrid backcross N1F2, respectively) or intermediate between the one expected for this compound at M(2) and M(3) receptors, (pK(B)=6.66+/-0.08, pA(2)=7.00+/-0.27 for female inbred strain C57BL/6). 4. These data study suggest that muscarinic M(3) receptors are the predominant, if not the exclusive, subtype mediating contractile responses to muscarinic agonists in female mouse urinary bladder smooth muscle, with strain differences.