Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Therapeutic Advances in Urology
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Lazzeri, M.
Right arrow Articles by Porena, M.
Right arrow Search for Related Content
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Reviews

Review: TRP family proteins in the lower urinary tract: translating basic science into new clinical prospective

Massimo Lazzeri

Department of Urology, Santa Chiara Hospital Piazza Indipendenza n° 11, 50129, Florence, Italy, lazzeri.m{at}tiscali.it

Elisabetta Costantini

Department of Medical-Surgical Specialties and Public Health, Urology and Andrology Section, University of Perugia, Italy

Massimo Porena

Department of Medical-Surgical Specialties and Public Health, Urology and Andrology Section, University of Perugia, Italy

The lower urinary tract (LUT) is densely innervated by capsaicin-sensitive primary afferent neurons, a sub set of sensory nerves, in a number of species including humans. These fibers exhibit both a sensory (afferent) function, including the regulation of the micturition reflex and the perception of pain, and an `efferent' function, involved in the detrusor smooth muscle contractility and plasma protein extravasation. The discovery of specific binding sites for capsaicin, the pungent ingredient of red chilli, initiated a rush that ended up with the cloning of the `vanilloid receptor', which belongs to the TRP (transient receptor potential) family. Here we reviewed the knowledge about the presumable functions of TRP family proteins in the LUT as regulators of bladder reflex activity, pain perception and cell differentiation. This review will focus on experimental evidence and promising clinical applications of targeting these proteins for the treatment of detrusor overactivity and bladder pain syndrome. As TRP receptor ligands may promote cellular death, and inhibit the growth of normal and neoplastic cells, the translation of basic science evidence into new clinical prospective for bladder and prostate cancer will be shown.

Key Words: sensory nerves • capsaicin • TRP family • TRPV1 • lower urinary tract • detrusor overactivity • bladder cancer • prostate cancer

References

  • Acs, G., Palkovits, M. and Blumberg, P.M. (1994) Comparison of [3H] resiniferatoxin binding by the vanilloid receptor in dorsal root ganglia, spinal cord, dorsal vagal complex, sciatic and vagal nerve and urinary bladder of the rat. Life Sci 55: 1017-26.[CrossRef][Medline] [Order article via Infotrieve]
  • Apostolidis, A., Popat, R., Yiangou, Y., Cockayne, D., Ford, A.P., Davis, J.B. et al. (2005) Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol 174: 977-82.[CrossRef][Medline] [Order article via Infotrieve]
  • Barbanti, G., Maggi, C.A., Beneforti, P., Baroldi, P. and Turini, D. (1993) Relief of pain following intravesical capsaicin in patients with hypersensitive disorders of the lower urinary tract. Br J Urol Int 71: 686-91.[CrossRef]
  • Bidaux, G., Flourakis, M., Thebault, S., Zholos, A., Beck, B., Gkika, D. et al. (2007) Differentiation status of prostate cells determines TRPM8 channel subcellular localization and function: involvement in carcinogenesis. J Clin Invest 117: 1647-57.[CrossRef][Medline] [Order article via Infotrieve]
  • Bidaux, G., Roudbaraki, M., Merle, C., Crepin, A., Delcourt, P. and Slomianny, C. (2005) Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement. Endocr-Relat Cancer 12: 367-82.[CrossRef]
  • Birder, L.A., Kanai, A.J., De Groat, W.C., Kiss, S., Nealan, M.L., Burke, N.E. et al. (2001) Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci USA 98: 13396-401.[Free Full Text]
  • Bödding, M. (2007) TRP proteins and cancer. Cell. Signal 19: 617-24.[CrossRef][Medline] [Order article via Infotrieve]
  • Bödding, M. and Flockerzi, V. (2004) Ca2+ dependence of the Ca2+-selective TRPV6 channel. J Biol Chem 279: 36546-52.[Abstract/Free Full Text]
  • Brady, C.M., Apostolidis, A.N., Harper, M., Yiangou, Y., Beckett, A., Jacques, T.S. et al. (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. Br J Urol Int 93: 770-6.
  • Caprodossi, S., Lucciarini, R., Amantini, C., Nabissi, M., Canesin, G., Ballarini, P. et al. (2008) Transient receptor potential vanilloid type 2 (TRPV2) expression in normal urothelium and in urothelial carcinoma of human bladder: correlation with the pathologic stage. Eur Urol 54: 612-20.[CrossRef][Medline] [Order article via Infotrieve]
  • Caterina, M.J., Schumacher, M.A., Tominaga, M., Rosen, T.A., Levine, J.D. and Julius, D. (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389: 816-24.[CrossRef][Medline] [Order article via Infotrieve]
  • Cruz, F., Guimarães, M., Silva, C., Rio, M.E., Coimbra, A. and Reis, M. (1997) Desensitization of bladder sensory fibers by intravesical capsaicin has long lasting clinical and urodynamic effects in patients with hyperactive or hypersensitive bladder dysfunction. J Urol 157: 585-9.[CrossRef][Medline] [Order article via Infotrieve]
  • de Groat, W.C. (1996) Nervous control of the urinary bladder in the cat. Brain Research 87: 201-11.
  • de Groat, W.C., Kawatani, M., Hisamitsu, T., Cheng, C.L., Ma, C.P., Thor, K. et al. (1990) Mechanisms underlying the recovery of urinary bladder function following spinal cord injury. Journal of Autonomic Nervous System 30(Suppl.): 571-7.
  • Dinis, P., Charrua, A., Avelino, A., Nagy, I., Quintas, J., Ribau, U. et al. (2005) The distribution of sensory fibers immunoreactive for the TRPV1 (capsaicin) receptor in the human prostate. Eur Urol 48: 162-7.[CrossRef][Medline] [Order article via Infotrieve]
  • Dinis, P., Charrua, A., Avelino, A., Yaqoob, M., Bevan, S., Nagy, I. et al. (2004) Anandamide-evoked activation of vanilloid receptor 1 contributes to the development of bladder hyperreflexia and nociceptive transmission to spinal dorsal horn neurons in cystitis. J Neurosci 24: 11253-63.[Abstract/Free Full Text]
  • Eisenberger, M.A., Blumenstein, B.A., Crawford, E.D., Miller, G., McLeod, D.G., Loehrer, P.J. et al. (1998) Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med 339: 1036-42.[Abstract/Free Full Text]
  • Fixemer, T., Wissenbach, U., Flockerzi, V. and Bonkhoff, H. (2003) Expression of the Ca2+-selective cation channel TRPV6 in human prostate cancer: a novel prognostic marker for tumour progression. Oncogene 22: 7858-61.[CrossRef][Medline] [Order article via Infotrieve]
  • Fowler, C.J., Jewkes, D., McDonald, W.I., Lynn, B. and de Groat, W.C. (1992) Intravesical capsaicin for neurogenic bladder dysfunction. Lancet 339: 1239.[Medline] [Order article via Infotrieve]
  • Fuessel, S., Sickert, D., Meye, A., Klenk, U., Schmidt, U., Schmitz, M. et al. (2003) Multiple tumour marker analyses (PSA, hK2, PSCA, trp-p8) in primary prostate cancers using quantitative RT-PCR. Int J Oncol 23: 221-8.[Medline] [Order article via Infotrieve]
  • Guerios, S.D., Wang, Z.Y. and Bjorling, D.E. (2006) Nerve growth factor mediates peripheral mechanical hypersensitivity that accompanies experimental cystitis in mice. Neurosci Lett 392: 193-7.[CrossRef][Medline] [Order article via Infotrieve]
  • Güler, A.D., Lee, H., Iida, T., Shimizu, I., Tominaga, M. and Caterina, M.J. (2002) Heat-evoked activation of the ion channel, TRPV4. J Neurosci 22: 6408-14.[Abstract/Free Full Text]
  • Harteneck, C. (2005) Function and pharmacology of TRPM cation channels. Naunyn-Schmiedeberg's Arch Pharmacol 371: 307-14.[CrossRef][Medline] [Order article via Infotrieve]
  • Henshall, S.M., Afar, D.E., Hiller, J., Horvath, L.G., Quinn, D.I., Rasiah, K.K. et al. (2003) Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse. Cancer Res 63: 4196-203.[Abstract/Free Full Text]
  • Ji, R.R., Samad, T.A., Jin, S.X., Schmoll, R. and Woolf, C.J. (2002) p38 MAPK activation in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36: 57-68.[CrossRef][Medline] [Order article via Infotrieve]
  • Jung, M.Y., Kang, H.J. and Moon, A. (2001) Capsaicin-induced apoptosis in SK-Hep-1 hepatocarcinoma cells involves Bcl-2 downregulation and caspase-3 activation. Cancer Lett 165: 139-45.[CrossRef][Medline] [Order article via Infotrieve]
  • Kiessling, A., Fussel, S., Schmitz, M., Stevanovic, S., Meye, A. and Weigle, B. (2003) Identification of an HLA-A*0201-restricted T-cell epitope derived from the prostate cancer-associated protein TRP-P8. Prostate 56: 270-9.[CrossRef][Medline] [Order article via Infotrieve]
  • Kim, J.C., Beckel, J.M., Birder, L.A., Kiss, S., Washabaugh, C., Kanai, A. et al. (2001) Identification of functional vanilloid receptors in human bladder urothelial cells using a nitric oxide microsensor technique and reverse transcriptase polymerase chain reaction. J Urol 165(Suppl. 5): 34.
  • Kuo, H.C. (2003) Effectiveness of intravesical resiniferatoxin in treating detrusor hyper-reflexia and external sphincter dyssynergia in patients with chronic spinal cord lesions. Br J Urol Int 92: 597-601.
  • Lazzeri, M., Vannucchi, M.G., Bizzocco, E., Spinelli, M., Beneforti, P., Turini, D. et al. (2005) Transient receptor potential vanilloid type 1 (TRPV1) expression changes from normal urothelium to transitional cell carcinoma of human bladder. Eur Urol 48: 691-8.[CrossRef][Medline] [Order article via Infotrieve]
  • Lazzeri, M., Beneforti, P., Spinelli, M., Zanollo, A., Barbagli, G. and Turini, D. (2000) Intravesical resiniferatoxin for the treatment of hypersensitive disorder: a randomized placebo controlled study. J Urol 164: 676-9.[CrossRef][Medline] [Order article via Infotrieve]
  • Lazzeri, M., Barbanti, G., Beneforti, P., Maggi, C.A., Taddei, I., Ungar, A. et al. (1995) Vesical-renal reflex: diuresis and natriuresis activated by intravesical capsaicin. Scand J Urol Nephrol 29: 39-43.[Medline] [Order article via Infotrieve]
  • Lecci, A. and Maggi, C.A. (2001) Tachykinins as modulators of the micturition reflex in the central and peripheral nervous system. Regul Peptides 101: 1-18.[CrossRef][Medline] [Order article via Infotrieve]
  • Lee, Y.S., Nam, D.H. and Kim, J.A. (2000) Induction of apoptosis by capsaicin in A172 human glioblastoma cells. Cancer Lett 161: 121-30.[CrossRef][Medline] [Order article via Infotrieve]
  • Liu, B. and Qin, F.J. (2005) Functional control of cold-menthol-sensitive TRPM8 ion channels by phosphatidylinositol 4,5-bisphosphate. Neuroscience 25: 1674-81.[CrossRef][Medline] [Order article via Infotrieve]
  • MacDiamid, J.A., Mugridge, N.B., Weiss, J.C., Phillips, L., Burn, A.L., Paulin, R.P. et al. (2007) Bacterially derived 400 nm particules for encapsulation and cancer cell targeting of chemotherapeutics. Cancer Cell 11: 431-45.[CrossRef][Medline] [Order article via Infotrieve]
  • Macho, A., Calzado, M.A., Munoz-Blanco, J., Goómez-Díaz, C., Gajate, C., Mollinedo, F. et al. (1999) Selective induction of apoptosis by capsaicin in transformed cells: the role of reactive oxygen species and calcium. Cell Death Differ 6: 155-65.[CrossRef][Medline] [Order article via Infotrieve]
  • Maggi, C.A., Barbanti, G., Santicioli, P., Beneforti, P., Misuri, D., Meli, A. et al. (1989) Cystometric evidence that capsaicin-sensitive nerves modulate the afferent branch of micturition reflex in humans. J Urol 142: 150-4.[Medline] [Order article via Infotrieve]
  • Maggi, C.A. and Meli, A. (1988) The sensory efferent function of capsaicin-sensitive neurons. Gen Pharmac 19: 1-43.[Medline] [Order article via Infotrieve]
  • Miller, L.J., Fischer, K.A., Goralnick, S.J., Litt, M., Burleson, J.A., Albertsen, P. et al. (2002) Nerve growth factor and chronic prostatitis/chronic pelvic pain syndrome. Urology 59: 603-8.[CrossRef][Medline] [Order article via Infotrieve]
  • Montell, C., Jones, K., Hafen, E. and Rubin, G. (1985) Rescue of the Drosophila phototransduction mutation trp by germline transformation. Science 230: 1040-3.[Abstract/Free Full Text]
  • Myers-Irvin, J.M., Van Le, T.S. and Getzenberg, R.H. (2005) Mechanistic Analysis of the Role of BLCA-4 in Bladder Cancer Pathobiology. Cancer Research 65: 7145-7150.[Abstract/Free Full Text]
  • Nilius, B., Owsianik, G., Voets, T. and Peters, J.A. (2007) Transient receptor cation channels in disease. Physiol Rev 87: 165-217.[Abstract/Free Full Text]
  • Payne, C.K., Mosbaugh, P.G., Forrest, J.B., Evans, R.J., Whitmore, K.E., Antoci, J.P. et al. (2005) Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial. J Urol 173: 1590-4.[CrossRef][Medline] [Order article via Infotrieve]
  • Peier, A.M., Moqrich, A., Hergarden, A.C., Reeve, A.J., Andersson, D.A., Story, G.M. et al. (2002) A TRP channel that senses cold stimuli and menthol. Cell 108: 705-15.[CrossRef][Medline] [Order article via Infotrieve]
  • Peng, J.B., Zhuang, L., Berger, U.V., Adam, R.M., Williams, B.J., Brown, E.M. et al. (2001) CaT1 expression correlates with tumour grade in prostate cancer. Biochem Biophys Res Commun 282: 729-34.[CrossRef][Medline] [Order article via Infotrieve]
  • Putney Jr, J.W. (2004) The enigmatic TRPCs: multifunctional cation channels. Trends Cell Biol 14: 282-6.[CrossRef][Medline] [Order article via Infotrieve]
  • Ramsey, S.I., Delling, M. and Clapham, D.E. (2006) An introduction to TRP channels. Ann Rev Physio 68: 18.1-18.29.
  • Reilly, C.A., Taylor, J.C., Lanza, D.L., Carr, B.A., Crouch, D.J. and Yost, G.S. (2003) Capsaicinoids cause inflammation and epithelial cell death through activation of vanilloid receptors. Toxicol Sci 73: 170-81.[Abstract/Free Full Text]
  • Silva, C., Silva, J., Ribeiro, M.J., Avelino, A. and Cruz, F. (2005) Urodynamic effect of intravesical resiniferatoxin in patients with neurogenic detrusor overactivity of spinal origin: results of a double-blind randomized placebo-controlled trial. Eur Urol 48: 650-5.[CrossRef][Medline] [Order article via Infotrieve]
  • Smart, D., Gunthorpe, M.J., Jerman, J.C., Nasir, S., Gray, J., Muir, A.I. et al. (2000) The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1). Br J Pharmacol 129: 227-30.[CrossRef][Medline] [Order article via Infotrieve]
  • Sydorenko, V., Shuba, Y., Thebault, S., Roudbaraki, M., Lepage, G., Prevarskaya, N. et al. (2003) Receptor-coupled, DAG-gated Ca2+-permeable cationic channels in LNCaP human prostate cancer epithelial cells. J Physiol 548: 823-36.[Abstract/Free Full Text]
  • Szallasi, A., Conte, B., Goso, C., Blumberg, P.M. and Manzini, S. (1993) Characterization of a peripheral vanilloid (capsaicin) receptor in the rat urinary bladder. Life Sci 52: PL221-PL226.[CrossRef][Medline] [Order article via Infotrieve]
  • Tapia-Vieyra, J.V. and Mas-Oliva, J. (2001) Apoptosis and cell death channels in prostate cancer. Arch Med Res 32: 175-85.[CrossRef][Medline] [Order article via Infotrieve]
  • Trevisani, M., Smart, D., Gunthorpe, M.J., Tognetto, M., Barbieri, M., Campi, B. et al. (2002) Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1. Nat Neurosci 5: 546-51.[CrossRef][Medline] [Order article via Infotrieve]
  • Tsavaler, L., Shapero, M.H., Morkowski, S. and Laus, R. (2001) Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res 61: 3760-9.[Abstract/Free Full Text]
  • Turini, D., Beneforti, P., Spinelli, M., Malagutti, S. and Lazzeri, M. (2006) Heat/burning sensation induced by topical application of capsaicin on perineal cutaneous area: new approach in diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome? Urology 67: 910-3.[CrossRef][Medline] [Order article via Infotrieve]
  • Vanden Abeele, F., Shuba, Y., Roudbaraki, M., Lemonnier, L., Vanoverberghe, K., Mariot, P. et al. (2003) Store-operated Ca2+ channels in prostate cancer epithelial cells: function, regulation, and role in carcinogenesis. Cell Calcium 33: 357-73.[CrossRef][Medline] [Order article via Infotrieve]
  • Wissenbach, U., Niemeyer, B.A., Fixemer, T., Schniedewind, A., Trost, C., Cavalie, A. et al. (2001) Expression of CaTlike, a novel calcium-selective channel, correlates with the malignancy of prostate cancer. J Biol Chem 276: 19461-8.[Abstract/Free Full Text]
  • Xu, H., Ramsey, I.S., Kotecha, S.A., Moran, M.M., Chong, J.A., Lawson, D. et al. (2002) TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418: 181-6.[CrossRef][Medline] [Order article via Infotrieve]
  • Zhang, L. and Barritt, G.J. (2006) TRPM8 in prostate cancer cells: a potential diagnostic and prognostic marker with a secretory function? Endocr-Relat Cancer 13: 27-38.[CrossRef]
  • Zhang, L. and Barritt, G.J. (2004) Evidence that TRPM8 is an androgen-dependent Ca2+ channel required for the survival of prostate cancer cells. Cancer Res 64: 8365-73.[Abstract/Free Full Text]
  • Zhang, L., Brereton, H.M., Hahn, M., Froscio, M., Tilley, W.D., Brown, M.P. et al. (2003) Expression of Drosophila Ca2+ permeable transient receptor potential-like channel protein in a prostate cancer cell line decreases cell survival. Cancer Gene Ther 10: 611-25.[CrossRef][Medline] [Order article via Infotrieve]
  • Zhu, Y., Wang, Y. and Wang, D.H. (2005) Diuresis and natriuresis caused by activation of VR1-positive sensory nerves in renal pelvis of rats. Hypertension 46: 992-7.[Abstract/Free Full Text]

Therapeutic Advances in Urology, Vol. 1, No. 1, 33-42 (2009)
DOI: 10.1177/1756287209103922


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Lazzeri, M.
Right arrow Articles by Porena, M.
Right arrow Search for Related Content
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?