Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 379, Issue 4, pp 421–425 | Cite as

Where is TRPV1 expressed in the bladder, do we see the real channel?

  • Wouter EveraertsEmail author
  • M. Rosario Sepúlveda
  • Thomas Gevaert
  • Tania Roskams
  • Bernd Nilius
  • Dirk De Ridder
Short Communication


Transient receptor potential channel-vanilloid subfamily member 1 (TRPV1) is an important target in the treatment of bladder overactivity. This receptor is suggested to function as a mechanosensor in the normal bladder and to mediate the development of bladder overactivity during cystitis. Our aim was to determine the cellular distribution of TRPV1 in mouse and rat bladder tissue. We used three different commercial TRPV1 antibodies to perform immunohistochemistry on bladder tissue from rats and wild-type and TRPV1−/− mice, using trigeminal ganglia as a control tissue for TRPV1 expression. Although two of the antibodies seemed to react specifically in trigeminal ganglion tissue, all the antibodies produced a similar staining pattern in the urothelium of wild-type and TRPV1−/− mice. These data show that TRPV1 antibodies can cause an aspecific immunostaining in bladder tissue, urging for additional research to confirm the exact distribution of TRPV1 in bladder. In conclusion, we think that the use of negative controls on knockout mice, whenever available, is mandatory when conducting immunohistochemical localization studies.


TRPV1 Bladder Immunohistochemistry Mouse Specificity 



We thank Paula Aertsen for excellent technical assistance. Wouter Everaerts is a doctoral fellow of the Fonds wetenschappelijke onderzoek Vlaanderen (FWO). This work was supported by FWO grant 0149.03.


  1. Apostolidis A, Brady CM, Yiangou Y, Davis J, Fowler CJ, Anand P (2005a) Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin. Urology 65:400–405PubMedCrossRefGoogle Scholar
  2. Apostolidis A, Popat R, Yiangou Y, Cockayne D, Ford AP, Davis JB, Dasgupta P, Fowler CJ, Anand P (2005b) Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol 174:977–982 discussion 982–973PubMedCrossRefGoogle Scholar
  3. Avelino A, Cruz F (2006) TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications. Naunyn Schmiedebergs Arch Pharmacol 373:287–299PubMedCrossRefGoogle Scholar
  4. Birder LA, Kanai AJ, de Groat WC, Kiss S, Nealen ML, Burke NE, Dineley KE, Watkins S, Reynolds IJ, Caterina MJ (2001) Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci USA 98:13396–13401PubMedCrossRefGoogle Scholar
  5. Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ, Wang E, Ruiz G, De Groat WC, Apodaca G, Watkins S, Caterina MJ (2002) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5:856–860PubMedCrossRefGoogle Scholar
  6. Brady CM, Apostolidis AN, Harper M, Yiangou Y, Beckett A, Jacques TS, Freeman A, Scaravilli F, Fowler CJ, Anand P (2004) Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment. BJU Int 93:770–776PubMedCrossRefGoogle Scholar
  7. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824PubMedCrossRefGoogle Scholar
  8. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313PubMedCrossRefGoogle Scholar
  9. Chancellor MB, de Groat WC (1999) Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder. J Urol 162:3–11PubMedCrossRefGoogle Scholar
  10. Charrua A, Cruz CD, Cruz F, Avelino A (2007) Transient receptor potential vanilloid subfamily 1 is essential for the generation of noxious bladder input and bladder overactivity in cystitis. J Urol 177:1537–1541PubMedCrossRefGoogle Scholar
  11. Charrua A, Reguenga C, Paule CC, Nagy I, Cruz F, Avelino A (2008) Cystitis is associated with TRPV1b-downregulation in rat dorsal root ganglia. Neuroreport 19:1469–1472PubMedCrossRefGoogle Scholar
  12. Charrua A, Cruz CD, Narayanan S, Gharat L, Gullapalli S, Cruz F, Avelino A (2009) GRC-6211, a new oral specific TRPV1 antagonist, decreases bladder overactivity and noxious bladder input in cystitis animal models. J Urol 181:379–386PubMedCrossRefGoogle Scholar
  13. De Ridder D, Baert L (2000) Vanilloids and the overactive bladder. BJU Int 86:172–180 quiz iiPubMedCrossRefGoogle Scholar
  14. Everaerts W, Gevaert T, Nilius B, De Ridder D (2008) On the origin of bladder sensing: Tr(i)ps in urology. Neurourol Urodyn 27:264–273PubMedCrossRefGoogle Scholar
  15. 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 117:3453–3462PubMedCrossRefGoogle Scholar
  16. Guo A, Vulchanova L, Wang J, Li X, Elde R (1999) Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. Eur J Neurosci 11:946–958PubMedCrossRefGoogle Scholar
  17. Hou M, Uddman R, Tajti J, Kanje M, Edvinsson L (2002) Capsaicin receptor immunoreactivity in the human trigeminal ganglion. Neurosci Lett 330:223–226PubMedCrossRefGoogle Scholar
  18. Lazzeri M, Vannucchi MG, Zardo C, Spinelli M, Beneforti P, Turini D, Faussone-Pellegrini MS (2004) Immunohistochemical evidence of vanilloid receptor 1 in normal human urinary bladder. Eur Urol 46:792–798PubMedCrossRefGoogle Scholar
  19. Lazzeri M, Vannucchi MG, Spinelli M, Bizzoco E, Beneforti P, Turini D, Faussone-Pellegrini MS (2005) Transient receptor potential vanilloid type 1 (TRPV1) expression changes from normal urothelium to transitional cell carcinoma of human bladder. Eur Urol 48:691–698PubMedCrossRefGoogle Scholar
  20. Liu HT, Kuo HC (2007) Increased expression of transient receptor potential vanilloid subfamily 1 in the bladder predicts the response to intravesical instillations of resiniferatoxin in patients with refractory idiopathic detrusor overactivity. BJU Int 100:1086–1090PubMedCrossRefGoogle Scholar
  21. Lorincz A, Nusser Z (2008) Specificity of immunoreactions: the importance of testing specificity in each method. J Neurosci 28:9083–9086PubMedCrossRefGoogle Scholar
  22. Nilius B, Owsianik G, Voets T, Peters JA (2007) Transient receptor potential cation channels in disease. Physiol Rev 87:165–217PubMedCrossRefGoogle Scholar
  23. Ost D, Roskams T, Van Der Aa F, De Ridder D (2002) Topography of the vanilloid receptor in the human bladder: more than just the nerve fibers. J Urol 168:293–297PubMedCrossRefGoogle Scholar
  24. Wang ZY, Wang P, Merriam FV, Bjorling DE (2008) Lack of TRPV1 inhibits cystitis-induced increased mechanical sensitivity in mice. Pain 139:158–167PubMedCrossRefGoogle Scholar
  25. Yamada T, Ugawa S, Ueda T, Ishida Y, Kajita K, Shimada S (2008) Differential localizations of the transient receptor potential channels TRPV4 and TRPV1 in the mouse urinary bladder. J Histochem Cytochem. doi: 10.1369/jhc.2008.951962
  26. Zarghooni S, Wunsch J, Bodenbenner M, Bruggmann D, Grando SA, Schwantes U, Wess J, Kummer W, Lips KS (2007) Expression of muscarinic and nicotinic acetylcholine receptors in the mouse urothelium. Life Sci 80:2308–2313PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Wouter Everaerts
    • 1
    Email author
  • M. Rosario Sepúlveda
    • 2
  • Thomas Gevaert
    • 1
    • 3
  • Tania Roskams
    • 3
  • Bernd Nilius
    • 4
  • Dirk De Ridder
    • 1
  1. 1.Department of Surgery, Laboratory of Experimental Urology, Campus GasthuisbergKU LeuvenLeuvenBelgium
  2. 2.Department of Molecular Cell Biology, Laboratory of Ca2+-transport ATPases, Campus GasthuisbergKU LeuvenLeuvenBelgium
  3. 3.Department of Morphology and Molecular PathologyUniversity Hospitals LeuvenLeuvenBelgium
  4. 4.Department of Molecular Cell Biology, Laboratory of Ion Channel Research, Campus GasthuisbergKU LeuvenLeuvenBelgium

Personalised recommendations