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 cystect...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2015-06-01
|
Series: | Journal of Pharmacological Sciences |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861315001036 |
id |
doaj-5700c36ede0b4c3199116e0b81fcdffb |
---|---|
record_format |
Article |
spelling |
doaj-5700c36ede0b4c3199116e0b81fcdffb2020-11-25T00:36:35ZengElsevierJournal of Pharmacological Sciences1347-86132015-06-011282657010.1016/j.jphs.2015.05.005The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasiaTomonori Yamanishi0Kanya Kaga1Miki Fuse2Chiharu Shibata3Takao Kamai4Tomoyuki Uchiyama5Department of Urology, Continence Center, Dokkyo Medical University, Tochgi, JapanDepartment of Urology, Continence Center, Dokkyo Medical University, Tochgi, JapanDepartment of Urology, Continence Center, Dokkyo Medical University, Tochgi, JapanDepartment of Urology, Continence Center, Dokkyo Medical University, Tochgi, JapanDepartment of Urology, Continence Center, Dokkyo Medical University, Tochgi, JapanDepartment of Neurology, Continence Center, Dokkyo Medical University, Tochgi, JapanThe 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.http://www.sciencedirect.com/science/article/pii/S1347861315001036Human bladderMuscarinic receptor subtypeDetrusor overactivityBenign prostatic hyperplasia |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tomonori Yamanishi Kanya Kaga Miki Fuse Chiharu Shibata Takao Kamai Tomoyuki Uchiyama |
spellingShingle |
Tomonori Yamanishi Kanya Kaga Miki Fuse Chiharu Shibata Takao Kamai Tomoyuki Uchiyama The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia Journal of Pharmacological Sciences Human bladder Muscarinic receptor subtype Detrusor overactivity Benign prostatic hyperplasia |
author_facet |
Tomonori Yamanishi Kanya Kaga Miki Fuse Chiharu Shibata Takao Kamai Tomoyuki Uchiyama |
author_sort |
Tomonori Yamanishi |
title |
The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia |
title_short |
The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia |
title_full |
The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia |
title_fullStr |
The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia |
title_full_unstemmed |
The role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia |
title_sort |
role of muscarinic receptor subtypes on carbachol-induced contraction of normal human detrusor and overactive detrusor associated with benign prostatic hyperplasia |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2015-06-01 |
description |
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. |
topic |
Human bladder Muscarinic receptor subtype Detrusor overactivity Benign prostatic hyperplasia |
url |
http://www.sciencedirect.com/science/article/pii/S1347861315001036 |
work_keys_str_mv |
AT tomonoriyamanishi theroleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia AT kanyakaga theroleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia AT mikifuse theroleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia AT chiharushibata theroleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia AT takaokamai theroleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia AT tomoyukiuchiyama theroleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia AT tomonoriyamanishi roleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia AT kanyakaga roleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia AT mikifuse roleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia AT chiharushibata roleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia AT takaokamai roleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia AT tomoyukiuchiyama roleofmuscarinicreceptorsubtypesoncarbacholinducedcontractionofnormalhumandetrusorandoveractivedetrusorassociatedwithbenignprostatichyperplasia |
_version_ |
1725304733161226240 |