Article date: August 2001
By: A Choppin, R M Eglen in Volume 133, Issue 7, pages 1035-1040
The pharmacological characteristics of muscarinic receptors in the male mice urinary bladder smooth muscle were studied.
(+)‐Cis‐dioxolane, oxotremorine‐M, acetylcholine, carbachol and pilocarpine induced concentration‐dependent contractions of the urinary bladder smooth muscle (pEC50=6.6±0.1, 6.9±0.1, 6.7±0.1, 5.8±0.1 and 5.8±0.1, EMax=3.2±0.8 g, 2.7±0.4 g, 1.0±0.1 g, 2.7±0.3 and 0.9±0.2 g, respectively, n=4). These contractions were competitively antagonized by a range of muscarinic receptor antagonists (pKB values): atropine (9.22±0.09), pirenzepine (6.85±0.08), 4‐DAMP (8.42±0.14), methoctramine (5.96±0.05), p‐F‐HHSiD (7.48±0.09), tolterodine (8.89±0.13), AQ‐RA 741 (7.04±0.12), s‐secoverine (8.21±0.09), zamifenacin (8.30±0.17) and darifenacin (8.70±0.09).
In this tissue, the pKB values correlated most favourably with pKi values for these compounds at human recombinant muscarinic M3 receptors. A significant correlation was also noted at human recombinant muscarinic m5 receptors given the poor discriminative ability of ligands between M3 and m5 receptors.
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=6.23±0.14; pA2=6.16±0.03).
Overall, these data study suggest that muscarinic M3 receptors are the predominant, if not the exclusive, subtype mediating contractile responses to muscarinic agonists in male mouse urinary bladder smooth muscle.
The pharmacological characteristics of muscarinic receptors in the male mice urinary bladder smooth muscle were studied.
(+)‐Cis‐dioxolane, oxotremorine‐M, acetylcholine, carbachol and pilocarpine induced concentration‐dependent contractions of the urinary bladder smooth muscle (pEC50=6.6±0.1, 6.9±0.1, 6.7±0.1, 5.8±0.1 and 5.8±0.1, EMax=3.2±0.8 g, 2.7±0.4 g, 1.0±0.1 g, 2.7±0.3 and 0.9±0.2 g, respectively, n=4). These contractions were competitively antagonized by a range of muscarinic receptor antagonists (pKB values): atropine (9.22±0.09), pirenzepine (6.85±0.08), 4‐DAMP (8.42±0.14), methoctramine (5.96±0.05), p‐F‐HHSiD (7.48±0.09), tolterodine (8.89±0.13), AQ‐RA 741 (7.04±0.12), s‐secoverine (8.21±0.09), zamifenacin (8.30±0.17) and darifenacin (8.70±0.09).
In this tissue, the pKB values correlated most favourably with pKi values for these compounds at human recombinant muscarinic M3 receptors. A significant correlation was also noted at human recombinant muscarinic m5 receptors given the poor discriminative ability of ligands between M3 and m5 receptors.
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=6.23±0.14; pA2=6.16±0.03).
Overall, these data study suggest that muscarinic M3 receptors are the predominant, if not the exclusive, subtype mediating contractile responses to muscarinic agonists in male mouse urinary bladder smooth muscle.
British Journal of Pharmacology (2001) 133, 1035–1040; doi:10.1038/sj.bjp.0704165
DOI: 10.1038/sj.bjp.0704165
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