title: The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia.
abstract: 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.
authors.affiliation: Department of Urology, Continence Center, Dokkyo Medical University, Tochgi, Japan. Electronic address: yamanish@dokkyomed.ac.jp.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yamanishi
authors.affiliation: Department of Urology, Continence Center, Dokkyo Medical University, Tochgi, Japan.
authors.forename: Kanya
authors.initials: K
authors.lastname: Kaga
authors.affiliation: Department of Urology, Continence Center, Dokkyo Medical University, Tochgi, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Fuse
authors.affiliation: Department of Urology, Continence Center, Dokkyo Medical University, Tochgi, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Shibata
authors.affiliation: Department of Urology, Continence Center, Dokkyo Medical University, Tochgi, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kamai
authors.affiliation: Department of Neurology, Continence Center, Dokkyo Medical University, Tochgi, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Uchiyama
mesh_terms: D002217:Carbachol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011470:Prostatic Hyperplasia / Q000150:complications* / Q000503:physiopathology*; D043587:Receptor, Muscarinic M3 / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects*; D053201:Urinary Bladder, Overactive / Q000209:etiology* / Q000503:physiopathology*
chemical_list: D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D043587:Receptor, Muscarinic M3; D002217:Carbachol
keywords: Benign prostatic hyperplasia; Detrusor overactivity; Human bladder; Muscarinic receptor subtype