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.
(+)‐Cis‐dioxolane, oxotremorine‐M, acetylcholine, carbachol and pilocarpine induced concentration‐dependent contractions of the urinary bladder smooth muscle (range for pEC50=6.4–6.6, 6.2–6.7, 6.2–6.4, 5.4–6.0 and 0.0–5.1, Tmax=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 (pKB 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).
In recontraction studies, in which the muscarinic M3 receptor population was decreased, and conditions optimized to study M2 receptor activation, methoctramine exhibited an affinity estimate consistent with muscarinic M3 receptors (pKB=6.26±0.08, pA2=6.31±0.07; pKB=6.09±0.22, pA2=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 M2 and M3 receptors, (pKB=6.66±0.08, pA2=7.00±0.27 for female inbred strain C57BL/6).
These data study suggest that muscarinic M3 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.
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.
(+)‐Cis‐dioxolane, oxotremorine‐M, acetylcholine, carbachol and pilocarpine induced concentration‐dependent contractions of the urinary bladder smooth muscle (range for pEC50=6.4–6.6, 6.2–6.7, 6.2–6.4, 5.4–6.0 and 0.0–5.1, Tmax=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 (pKB 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).
In recontraction studies, in which the muscarinic M3 receptor population was decreased, and conditions optimized to study M2 receptor activation, methoctramine exhibited an affinity estimate consistent with muscarinic M3 receptors (pKB=6.26±0.08, pA2=6.31±0.07; pKB=6.09±0.22, pA2=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 M2 and M3 receptors, (pKB=6.66±0.08, pA2=7.00±0.27 for female inbred strain C57BL/6).
These data study suggest that muscarinic M3 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.
British Journal of Pharmacology (2002) 137, 522–528. doi:10.1038/sj.bjp.0704897
DOI: 10.1038/sj.bjp.0704897
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