Tomohiko Kamasako1, Kanya Kaga1, Mayuko Kaga1, Miki Fuse1, Mitsuru Ishizuka2 and Tomonori Yamanishi1*
1Department of Urology, Continence Center, Dokkyo Medical University, Tochigi, Japan
2Department of Surgery, Continence Center, Dokkyo Medical University, Tochigi, Japan
Background and Objective: Cholinergic drugs have been considered for the treatment of underactive bladder; however, they have not been standardized due to lack of efficacy and serious side effects. This study examined the effects of pilocarpine, a muscarinic receptor agonist, on contraction of pig and human urinary bladder. Materials and Methods: Strips of bladder tissues were mounted in 10-ml organ baths containing Krebs solution, which was maintained at 37°C and continuously gassed with 95% O2 and 5% CO2. Cumulative Concentration-Response Curves (CRCs) to pilocarpine were obtained, in the presence of Krebs solution containing darifenacin, 4-Diphenyl Acetoxy-Methyl Piperidine Methiodide (4- DAMP) (M3 selective antagonist), pirenzepine (M1 selective antagonist), methoctramine (M2 selective antagonist), or in the presence of vehicle. Results: Pilocarpine induced contractions of smooth muscle of the detrusor in a concentrationdependent manner, with maximum contraction relative to 80 mM KCl of 134.4% and 78%, respectively, and pEC50 values of 5.28 and 5.1, respectively, in the pig and human bladder. Darifenacin, 4-DAMP, pirenzepine, and methoctramine caused surmountable antagonism of responses to pilocarpine, with Schild plot slopes of 1.37 ± 0.20, 0.80 ± 0.54, 1.05 ± 0.30, and 0.91 ± 0.35, respectively, in the pig bladder. The rank order of mean pA2 values was as follows: 4-DAMP (8.79 ± 0.27) = darifenacin (8.73 ± 0.06) > pirenzepine (6.72 ± 0.12) > methoctramine (6.58 ± 0.16). Darifenacin caused surmountable antagonism of responses to pilocarpine, with Schild plot slope of 0.93 ± 0.30 and a pA2 value of 8.85 ± 0.13 in the human bladder. Conclusion: Pilocarpine appears to produce contraction of the pig and human bladder through activation of M3-muscarinic receptor.
Kamasako T, Kaga K, Kaga M, Fuse M, Ishizuka M, Yamanishi T. Effects of Pilocarpine, a Muscarinic Receptor Agonist, on Contraction of the Pig and Human Urinary Bladder. Clin Surg. 2020; 5: 2898..