Skip to main content
Top
Published in: World Journal of Urology 3/2014

01-06-2014 | Original Article

Expression of transient receptor potential vanilloid 4 and effects of ruthenium red on detrusor overactivity associated with bladder outlet obstruction in rats

Authors: Kang Jun Cho, Eun Young Park, Hyo Sin Kim, Jun Sung Koh, Joon Chul Kim

Published in: World Journal of Urology | Issue 3/2014

Login to get access

Abstract

Purpose

To investigate transient receptor potential vanilloid 4 (TRPV4) expression and the effects of ruthenium red (RR)—TRPV antagonist—on detrusor overactivity (DO) associated with bladder outlet obstruction (BOO).

Methods

Rats were randomly assigned to 3 groups. The control group (n = 10) included sham-operated rats. The BOO-group without RR (n = 15) and BOO-group with RR (n = 15) underwent partial BOO surgery. Three weeks postoperatively, cystometrography was performed in all rats. After confirming DO, RR was instilled intravesically in the BOO-group with RR. Urodynamic parameters were investigated, including contraction interval (CI) and contraction pressure (CP). TRPV4 expression was evaluated through immunofluorescence staining and western blotting.

Results

The BOO-group without RR had significantly shorter CI and significantly higher CP compared to the control. In the BOO-group with RR, CI was significantly longer compared to the BOO-group without RR. However, change in CP between BOO-group without and with RR was not significantly different. Immunofluorescence staining showed that TRPV4 was localized in the urothelium and detrusor muscles. TRPV4 immunofluorescence signals were increased in the urothelium and detrusor muscle in BOO-group without RR, compared with the control. In western blot analysis, immunoreactive bands indicating expression of TRPV4 were detected in the urothelium and detrusor muscle, and those were significantly increased in the BOO-group without RR compared with the control in the urothelium and detrusor muscle.

Conclusions

TRPV4 plays an important role in the pathophysiology of DO, and RR has a beneficial effect on DO associated with BOO.
Literature
1.
go back to reference de Nunzio C, Franco G, Rocchegiani A, Iori F, Leonardo C, Laurenti C (2003) The evolution of detrusor overactivity after watchful waiting, medical therapy and surgery in patients with bladder outlet obstruction. J Urol 169:535–539PubMedCrossRef de Nunzio C, Franco G, Rocchegiani A, Iori F, Leonardo C, Laurenti C (2003) The evolution of detrusor overactivity after watchful waiting, medical therapy and surgery in patients with bladder outlet obstruction. J Urol 169:535–539PubMedCrossRef
2.
go back to reference Housami F, Abrams P (2008) Persistent detrusor overactivity after transurethral resection of the prostate. Curr Urol Rep 9:284–290PubMedCrossRef Housami F, Abrams P (2008) Persistent detrusor overactivity after transurethral resection of the prostate. Curr Urol Rep 9:284–290PubMedCrossRef
3.
go back to reference Yoshimura N (2007) Lower urinary tract symptoms (LUTS) and bladder afferent activity. Neurourol Urodyn 26:908–913PubMedCrossRef Yoshimura N (2007) Lower urinary tract symptoms (LUTS) and bladder afferent activity. Neurourol Urodyn 26:908–913PubMedCrossRef
4.
go back to reference Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999) A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398:436–441PubMedCrossRef Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999) A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398:436–441PubMedCrossRef
5.
go back to reference Benham CD, Davis JB, Randall AD (2002) Vanilloid and TRP channels: a family of lipid-gated cation channels. Neuropharmacology 42:873–888PubMedCrossRef Benham CD, Davis JB, Randall AD (2002) Vanilloid and TRP channels: a family of lipid-gated cation channels. Neuropharmacology 42:873–888PubMedCrossRef
6.
go back to reference Ha US, Park EY, Kim JC (2011) Effect of botulinum toxin on expression of nerve growth factor and transient receptor potential vanilloid 1 in urothelium and detrusor muscle of rats with bladder outlet obstruction-induced detrusor overactivity. Urology 78:721 e721–721 e726CrossRef Ha US, Park EY, Kim JC (2011) Effect of botulinum toxin on expression of nerve growth factor and transient receptor potential vanilloid 1 in urothelium and detrusor muscle of rats with bladder outlet obstruction-induced detrusor overactivity. Urology 78:721 e721–721 e726CrossRef
7.
go back to reference Yamada T, Ugawa S, Ueda T, Ishida Y, Kajita K, Shimada S (2009) Differential localizations of the transient receptor potential channels TRPV4 and TRPV1 in the mouse urinary bladder. J Histochem Cytochem 57:277–287PubMedCentralPubMedCrossRef Yamada T, Ugawa S, Ueda T, Ishida Y, Kajita K, Shimada S (2009) Differential localizations of the transient receptor potential channels TRPV4 and TRPV1 in the mouse urinary bladder. J Histochem Cytochem 57:277–287PubMedCentralPubMedCrossRef
8.
go back to reference Gevaert T, Vriens J, Segal A, Everaerts W, Roskams T, Talavera K, Owsianik G, Liedtke W, Daelemans D, Dewachter I, Van Leuven F, Voets T, De Ridder D, Nilius B (2007) Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J Clin Invest 117:3453–3462PubMedCentralPubMedCrossRef Gevaert T, Vriens J, Segal A, Everaerts W, Roskams T, Talavera K, Owsianik G, Liedtke W, Daelemans D, Dewachter I, Van Leuven F, Voets T, De Ridder D, Nilius B (2007) Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J Clin Invest 117:3453–3462PubMedCentralPubMedCrossRef
9.
10.
go back to reference Everaerts W, Vriens J, Owsianik G, Appendino G, Voets T, De Ridder D, Nilius B (2010) Functional characterization of transient receptor potential channels in mouse urothelial cells. Am J Physiol Renal Physiol 298:F692–F701PubMedCentralPubMedCrossRef Everaerts W, Vriens J, Owsianik G, Appendino G, Voets T, De Ridder D, Nilius B (2010) Functional characterization of transient receptor potential channels in mouse urothelial cells. Am J Physiol Renal Physiol 298:F692–F701PubMedCentralPubMedCrossRef
11.
go back to reference Thorneloe KS, Sulpizio AC, Lin Z, Figueroa DJ, Clouse AK, McCafferty GP, Chendrimada TP, Lashinger ES, Gordon E, Evans L, Misajet BA, Demarini DJ, Nation JH, Casillas LN, Marquis RW, Votta BJ, Sheardown SA, Xu X, Brooks DP, Laping NJ, Westfall TD (2008) N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1 -piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: part I. J Pharmacol Exp Ther 326:432–442PubMedCrossRef Thorneloe KS, Sulpizio AC, Lin Z, Figueroa DJ, Clouse AK, McCafferty GP, Chendrimada TP, Lashinger ES, Gordon E, Evans L, Misajet BA, Demarini DJ, Nation JH, Casillas LN, Marquis RW, Votta BJ, Sheardown SA, Xu X, Brooks DP, Laping NJ, Westfall TD (2008) N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1 -piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide (GSK1016790A), a novel and potent transient receptor potential vanilloid 4 channel agonist induces urinary bladder contraction and hyperactivity: part I. J Pharmacol Exp Ther 326:432–442PubMedCrossRef
12.
go back to reference Vlaskovska M, Kasakov L, Rong W, Bodin P, Bardini M, Cockayne DA, Ford AP, Burnstock G (2001) P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci 21:5670–5677PubMed Vlaskovska M, Kasakov L, Rong W, Bodin P, Bardini M, Cockayne DA, Ford AP, Burnstock G (2001) P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J Neurosci 21:5670–5677PubMed
13.
go back to reference Mochizuki T, Sokabe T, Araki I, Fujishita K, Shibasaki K, Uchida K, Naruse K, Koizumi S, Takeda M, Tominaga M (2009) The TRPV4 cation channel mediates stretch-evoked Ca2 + influx and ATP release in primary urothelial cell cultures. J Biol Chem 284:21257–21264PubMedCentralPubMedCrossRef Mochizuki T, Sokabe T, Araki I, Fujishita K, Shibasaki K, Uchida K, Naruse K, Koizumi S, Takeda M, Tominaga M (2009) The TRPV4 cation channel mediates stretch-evoked Ca2 + influx and ATP release in primary urothelial cell cultures. J Biol Chem 284:21257–21264PubMedCentralPubMedCrossRef
14.
go back to reference Janssen DA, Hoenderop JG, Jansen KC, Kemp AW, Heesakkers JP, Schalken JA (2011) The mechanoreceptor TRPV4 is localized in adherence junctions of the human bladder urothelium: a morphological study. J Urol 186:1121–1127PubMedCrossRef Janssen DA, Hoenderop JG, Jansen KC, Kemp AW, Heesakkers JP, Schalken JA (2011) The mechanoreceptor TRPV4 is localized in adherence junctions of the human bladder urothelium: a morphological study. J Urol 186:1121–1127PubMedCrossRef
15.
go back to reference Aizawa N, Wyndaele JJ, Homma Y, Igawa Y (2012) Effects of TRPV4 cation channel activation on the primary bladder afferent activities of the rat. Neurourol Urodyn 31:148–155PubMedCrossRef Aizawa N, Wyndaele JJ, Homma Y, Igawa Y (2012) Effects of TRPV4 cation channel activation on the primary bladder afferent activities of the rat. Neurourol Urodyn 31:148–155PubMedCrossRef
16.
go back to reference Everaerts W, Nilius B, Owsianik G (2010) The vanilloid transient receptor potential channel TRPV4: from structure to disease. Prog Biophys Mol Biol 103:2–17PubMedCrossRef Everaerts W, Nilius B, Owsianik G (2010) The vanilloid transient receptor potential channel TRPV4: from structure to disease. Prog Biophys Mol Biol 103:2–17PubMedCrossRef
17.
go back to reference Maggi CA, Giuliani S, Meli A (1989) Effect of ruthenium red on responses mediated by activation of capsaicin-sensitive nerves of the rat urinary bladder. Naunyn Schmiedebergs Arch Pharmacol 340:541–546PubMed Maggi CA, Giuliani S, Meli A (1989) Effect of ruthenium red on responses mediated by activation of capsaicin-sensitive nerves of the rat urinary bladder. Naunyn Schmiedebergs Arch Pharmacol 340:541–546PubMed
18.
go back to reference Juszczak K, Ziomber A, Thor PJ (2011) Effect of partial and complete blockade of vanilloid (TRPV1-6) and ankyrin (TRPA1) transient receptor potential ion channels on urinary bladder motor activity in an experimental hyperosmolar overactive bladder rat model. J Physiol Pharmacol 62:321–326PubMed Juszczak K, Ziomber A, Thor PJ (2011) Effect of partial and complete blockade of vanilloid (TRPV1-6) and ankyrin (TRPA1) transient receptor potential ion channels on urinary bladder motor activity in an experimental hyperosmolar overactive bladder rat model. J Physiol Pharmacol 62:321–326PubMed
19.
go back to reference Birder L, Kullmann FA, Lee H, Barrick S, de Groat W, Kanai A, Caterina M (2007) Activation of urothelial transient receptor potential vanilloid 4 by 4alpha-phorbol 12,13-didecanoate contributes to altered bladder reflexes in the rat. J Pharmacol Exp Ther 323:227–235PubMedCentralPubMedCrossRef Birder L, Kullmann FA, Lee H, Barrick S, de Groat W, Kanai A, Caterina M (2007) Activation of urothelial transient receptor potential vanilloid 4 by 4alpha-phorbol 12,13-didecanoate contributes to altered bladder reflexes in the rat. J Pharmacol Exp Ther 323:227–235PubMedCentralPubMedCrossRef
20.
go back to reference Everaerts W, Zhen X, Ghosh D, Vriens J, Gevaert T, Gilbert JP, Hayward NJ, McNamara CR, Xue F, Moran MM, Strassmaier T, Uykal E, Owsianik G, Vennekens R, De Ridder D, Nilius B, Fanger CM, Voets T (2010) Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis. Proc Natl Acad Sci USA 107:19084–19089PubMedCentralPubMedCrossRef Everaerts W, Zhen X, Ghosh D, Vriens J, Gevaert T, Gilbert JP, Hayward NJ, McNamara CR, Xue F, Moran MM, Strassmaier T, Uykal E, Owsianik G, Vennekens R, De Ridder D, Nilius B, Fanger CM, Voets T (2010) Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis. Proc Natl Acad Sci USA 107:19084–19089PubMedCentralPubMedCrossRef
Metadata
Title
Expression of transient receptor potential vanilloid 4 and effects of ruthenium red on detrusor overactivity associated with bladder outlet obstruction in rats
Authors
Kang Jun Cho
Eun Young Park
Hyo Sin Kim
Jun Sung Koh
Joon Chul Kim
Publication date
01-06-2014
Publisher
Springer Berlin Heidelberg
Published in
World Journal of Urology / Issue 3/2014
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-013-1099-y

Other articles of this Issue 3/2014

World Journal of Urology 3/2014 Go to the issue