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• W2084079850 abstract "The pharmacological characteristics of muscarinic receptors mediating contraction of dog isolated ciliary muscle were determined and compared to those mediating contraction of dog urinary bladder smooth muscle. (+)‐Cis‐dioxolane induced concentration‐dependent contractions of ciliary muscle (pEC 50 =7.18±0.07, E max =453±64 mg, n =19) and urinary bladder isolated smooth muscle (pEC 50 =6.55±0.07, E max =11±1 g, n =19). These responses were antagonized by several muscarinic receptor antagonists (p K b values for the ciliary muscle and the bladder smooth muscle, respectively): atropine (8.25±0.14 and 9.21±0.09), pirenzepine (6.31±0.13 and 6.70±0.25), tolterodine (7.97±0.14 and 8.68±0.12), oxybutynin (7.40±0.08 and 7.88±0.12), zamifenacin (6.46±0.19 and 7.69±0.11), S‐secoverine (6.66±0.14 and 8.13±0.07), AQ‐RA 741 (6.16±0.15 and 7.08±0.23), p‐F‐HHSiD (7.10±0.27 and 7.35±0.07) and responses were not antagonized by PD 102807 (up to 100 n M ). In urinary bladder smooth muscle, the profile of antagonist p K B values correlated significantly with p K i values at human recombinant m 3 muscarinic receptors, suggesting that M 3 muscarinic receptors mediated the response. In the ciliary muscle, a significant ( P <0.01) correlation was obtained with human recombinant m 3 and m 5 receptors. Darifenacin displayed insurmountable antagonism at receptors in the bladder. At receptors in the ciliary muscle, it exhibited two phases of antagonism, comprising an initial low affinity (p K B <6) component and a high affinity phase (p K B >8). The role of pigmentation in the atypical behaviour of darifenacin was examined. In blue coloured eyes, darifenacin produced apparent surmountable, competitive antagonism of the responses to (+)‐cis‐dioxolane (p K B =8.76±0.07). The antagonist profile obtained in this tissue suggested the involvement of a site which has the pharmacological attributes of the M 5 receptor. We suggest that the dog urinary bladder contracts in response to M 3 muscarinic receptor activation. Contraction of the brown‐eyed dog ciliary muscle is more complex and may include involvement of at least two receptors, possibly the M 5 and M 3 receptor, whereas blue‐eyed dog ciliary muscle may involve a single population of M 5 muscarinic receptors. British Journal of Pharmacology (2001) 132 , 835–842; doi: 10.1038/sj.bjp.0703901" @default.
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• W2084079850 date "2001-02-01" @default.
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• W2084079850 title "Pharmacological characterization of muscarinic receptors in dog isolated ciliary and urinary bladder smooth muscle" @default.
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• W2084079850 doi "https://doi.org/10.1038/sj.bjp.0703901" @default.
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