Pharmacological characterization of muscarinic receptors in dog isolated ciliary and urinary bladder smooth muscle

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 (pEC50=7.18±0.07, Emax=453±64 mg, n=19) and urinary bladder isolated smooth muscle (pEC50=6.55±0.07, Emax=11±1 g, n=19). These responses were antagonized by several muscarinic receptor antagonists (pKb 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 nM). In urinary bladder smooth muscle, the profile of antagonist pKB values correlated significantly with pKi values at human recombinant m3 muscarinic receptors, suggesting that M3 muscarinic receptors mediated the response. In the ciliary muscle, a significant (P