The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia

The aim of this study was to compare the effect of antimuscarinic antagonists on carbachol-induced contraction of normal human bladder and detrusor overactivity associated with benign prostatic hyperplasia (do/bph). samples of human bladder muscle were obtained from patients undergoing total cystectomy for bladder cancer (normal bladder),and those undergoing retropubic prostatectomy for bph. all of the patients with do/bph had detrusor overactivity according to urodynamic studies. detrusor muscle strips were mounted in 10-ml organ baths containing krebs solution,and concentration-response curves for carbachol were obtained in the presence of antimuscarinic antagonists (4-damp,methoctramine,pirenzepine,tolterodine,solifenacin,trospium,propiverine,oxybutynin,and imidafenacin) or vehicle. all antagonists competitively antagonized concentration-response curves to carbachol with high affinities in normal bladder. the rank order of mean pa2 values was as follows: trospium (10.1) > 4-damp (9.87),imidafenacin (9.3) > solifenacin (8.8) > tolterodine (8.6) > oxybutynin (8.3) > propiverine (7.7) > pirenzepine (7.4) > methoctramine (6.6). the effects of these antimuscarinic antagonists did not change when tested with do/bph bladder,suggesting that each antimuscarinic antagonist has a similar effect in this condition. schild plots showed a slope corresponding to unity,except for propiverine with do/bph detrusor. in conclusion,m3-receptors mainly mediate contractions in human bladder strips with normal state and do/bph. © 2015 the authors. production and hosting by elsevier b.v. on behalf of japanese pharmacologicalsociety. this is an open access article under the cc by-nc-nd license.