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TRP Channels in Drug Discovery pp 373–395Cite as

TRP Channels in the Genitourinary Tract

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Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Recently, TRP channels have been implicated in numerous pathologies of the genitourinary (GU) tract. TRP channels are differently expressed along the GU tract, and several lines of evidence suggest that they also have different roles in the pathophysiology of GU tract diseases. In this chapter, we focus on the expression and role of TRP in the urinary bladder and give an overall idea of TRP channel expression and function in the remaining GU tract.

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References

  1. Andersson KE, Gratzke C, Hedlund P (2010) The role of the transient receptor potential (TRP) superfamily of cation-selective channels in the management of the overactive bladder. BJU Int 106:1114–1127

    Article  PubMed  CAS  Google Scholar 

  2. Avelino A, Cruz C, Nagy I et al (2002) Vanilloid receptor 1 expression in the rat urinary tract. Neuroscience 109:787–798

    Article  PubMed  CAS  Google Scholar 

  3. Lazzeri M, Vannucchi MG, Zardo C et al (2004) Immunohistochemical evidence of vanilloid receptor 1 in normal human urinary bladder. Eur Urol 46:792–798

    Article  PubMed  CAS  Google Scholar 

  4. Saleh HA (2006) Vanilloid receptor type 1-immunoreactive nerves in the rat urinary bladder and primary afferent neurones: the effects of age. Folia Morphol (Warsz) 65:213–220

    CAS  Google Scholar 

  5. Gevaert T, Vriens J, Segal A et al (2010) Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J Clin Invest 117:3453–3462

    Article  CAS  Google Scholar 

  6. Cao DS, Yu SQ, Premkumar LS (2009) Modulation of transient receptor potential vanilloid 4-mediated membrane currents and synaptic transmission by protein kinase C. Mol Pain 5:5–17

    Article  PubMed  CAS  Google Scholar 

  7. Yamada T, Ugawa S, Ueda T (2009) Differential localizations of the transient receptor potential channels TRPV4 and TRPV1 in the mouse urinary bladder. J Histochem Cytochem 57:277–287

    Article  PubMed  CAS  Google Scholar 

  8. Charrua A, Cruz CD, Cruz F (2012) TRPV1 and TRPV4 antagonists have synergistic effect for treating bladder overactivity in rats. 27th Annual meeting EAU, Paris (accepted)

    Google Scholar 

  9. Stein RJ, Santos S, Nagatomi J et al (2004) Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol 172:1151–1178

    Article  Google Scholar 

  10. Streng T, Axelsson HE, Hedlund P et al (2008) Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol 53:391–399

    Article  PubMed  CAS  Google Scholar 

  11. Tsukimi Y, Mizuyachi K, Yamasaki T et al (2005) Cold response of the bladder in guinea pig: involvement of transient receptor potential channel, TRPM8. Urology 65:406–410

    Article  PubMed  Google Scholar 

  12. Mukerji G, Yiangou Y, Corcoran SL et al (2006) Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations. BMC Urol 6:6–16

    Article  PubMed  CAS  Google Scholar 

  13. Hayashi T, Kondo T, Ishimatsu M et al (2009) Expression of the TRPM8-immunoreactivity in dorsal root ganglion neurons innervating the rat urinary bladder. Neurosci Res 65:245–251

    Article  PubMed  CAS  Google Scholar 

  14. Everaerts W, Vriens J, Owsianik G et al (2010) Functional characterization of transient receptor potential channels in mouse urothelial cells. Am J Physiol Renal Physiol 298:F692–F701

    Article  PubMed  CAS  Google Scholar 

  15. Birder LA, Kanai AJ, de Groat WC et al (2001) Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci USA 98:13396–13401

    Article  PubMed  CAS  Google Scholar 

  16. Charrua A, Reguenga C, Cordeiro JM et al (2009) Functional transient receptor potential vanilloid 1 is expressed in human urothelial cells. J Urol 182:2944–2950

    Article  PubMed  CAS  Google Scholar 

  17. Birder L, Kullmann FA, Lee H et al (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 323:227–235

    Article  PubMed  CAS  Google Scholar 

  18. Kullmann FA, Shah MA, Birder LA et al (2009) Functional TRP and ASIC-like channels in cultured urothelial cells from the rat. Am J Physiol Renal Physiol 296:F892–F901

    Article  PubMed  CAS  Google Scholar 

  19. Yu W, Hill WG, Apodaca G et al (2010) Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium. Am J Physiol Renal Physiol 300:F49–F59

    Article  PubMed  CAS  Google Scholar 

  20. Janssen DA, Hoenderop JG, Jansen KC et al (2011) The mechanoreceptor TRPV4 is localized in adherence junctions of the human bladder urothelium: a morphological study. J Urol 186:1121–1127

    Article  PubMed  CAS  Google Scholar 

  21. Caprodossi S, Lucciarini R, Amantini C 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 54:612–620

    Article  PubMed  CAS  Google Scholar 

  22. Thorneloe KS, Sulpizio AC, Lin Z et al (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 326:432–442

    Article  PubMed  CAS  Google Scholar 

  23. Kobayashi H, Yoshiyama M, Zakoji H et al (2009) Sex differences in the expression profile of acid-sensing ion channels in the mouse urinary bladder: a possible involvement in irritative bladder symptoms. BJU Int 104:1746–1751

    Article  PubMed  CAS  Google Scholar 

  24. Birder LA, Nakamura Y, Kiss S et al (2002) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5:856–860

    Article  PubMed  CAS  Google Scholar 

  25. Charrua A, Cruz CD, Cruz F et al (2007) Transient receptor potential vanilloid subfamily 1 is essential for the generation of noxious bladder input and bladder overactivity in cystitis. J Urol 177:1537–1541

    Article  PubMed  CAS  Google Scholar 

  26. Charrua A, Cruz CD, Narayanan S et al (2009) GRC-6211, a new oral specific TRPV1 antagonist, decreases bladder overactivity and noxious bladder input in cystitis animal models. J Urol 181:379–386

    Article  PubMed  CAS  Google Scholar 

  27. Charrua A, Boudes M, De Ridder D, Cruz CD, Cruz F (2012) TRPV1 and TRPV4 expression in bladder neurons during normal condition and during cystitis. 27th Annual meeting EAU, Paris (accepted)

    Google Scholar 

  28. Lashinger ES, Steiginga MS, Hieble JP et al (2008) AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome. Am J Physiol Renal Physiol 295:F803–F810

    Article  PubMed  CAS  Google Scholar 

  29. McKemy DD, Neuhausser WM, Julius D (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416:52–58

    Article  PubMed  CAS  Google Scholar 

  30. Peier AM, Moqrich A, Hergarden AC et al (2002) A TRP channel that senses cold stimuli and menthol. Cell 108:705–715

    Article  PubMed  CAS  Google Scholar 

  31. Shibata Y, Ugawa S, Imura M et al (2011) TRPM8-expressing dorsal root ganglion neurons project dichotomizing axons to both skin and bladder in rats. Neuroreport 22:61–67

    Article  PubMed  CAS  Google Scholar 

  32. Sui GP, Wu C, Roosen A et al (2008) Modulation of bladder myofibroblast activity: implications for bladder function. Am J Physiol Renal Physiol 295:F688–F697

    Article  PubMed  CAS  Google Scholar 

  33. Fowler CJ, Jewkes D, McDonald WI et al (1992) Intravesical capsaicin for neurogenic bladder dysfunction. Lancet 339:1239

    Article  PubMed  CAS  Google Scholar 

  34. Cruz F, Guimarães M, Silva C et al (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 157:585–589

    Article  PubMed  CAS  Google Scholar 

  35. Geirsson G, Fall M, Sullivan L (1995) Clinical and urodynamic effects of intravesical capsaicin treatment in patients with chronic traumatic spinal detrusor hyperreflexia. J Urol 154:1825–1829

    Article  PubMed  CAS  Google Scholar 

  36. Das A, Chancellor MB, Watanabe T et al (1996) Intravesical capsaicin in neurologic impaired patients with detrusor hyperreflexia. J Spinal Cord Med 19:190–193

    PubMed  CAS  Google Scholar 

  37. De Séze M, Wiart L, Joseph PA et al (1998) Capsaicin and neurogenic detrusor hyperreflexia. A double blind placebo controlled study in 20 patients with spinal cord lesions. Neurourol Urodyn 17:513–523

    Article  PubMed  Google Scholar 

  38. Lazzeri M, Spinelli M, Beneforti P et al (1998) Intravesical resiniferatoxin for the treatment of detrusor hyperreflexia refractory to capsaicin in patients with chronic spinal cord diseases. Scand J Urol Nephrol 32:331–334

    Article  PubMed  CAS  Google Scholar 

  39. Kuo HC (2003) Effectiveness of intravesical resiniferatoxin in treating detrusor hyper-reflexia and external sphincter dyssynergia in patients with chronic spinal cord lesions. BJU Int 92:597–601

    Article  PubMed  CAS  Google Scholar 

  40. Silva C, Silva J, Ribeiro MJ (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 48:650–655

    Article  PubMed  CAS  Google Scholar 

  41. Kuo HC (2005) Multiple intravesical instillation of low-dose resiniferatoxin is effective in the treatment of detrusor overactivity refractory to anticholinergics. BJU Int 95:1023–1027

    Article  PubMed  CAS  Google Scholar 

  42. Chai TC, Gray ML, Steers W (1998) The incidence of a positive ice water test in bladder outlet obstructed patients: evidence for bladder neural plasticity. J Urol 160:34–38

    Article  PubMed  CAS  Google Scholar 

  43. Fowler CJ, Beck RO, Gerrard S et al (1994) Intravesical capsaicin for treatment of detrusor hyperreflexia. J Neurol Neurosurg Psychiatry 57:169–173

    Article  PubMed  CAS  Google Scholar 

  44. De Ridder D, Chandiramani V, Dasgupta P et al (1997) Intravesical capsaicin as a treatment for refractory detrusor hyperreflexia: a dual center study with long-term followup. J Urol 158:2087–2092

    Article  PubMed  Google Scholar 

  45. Cruz F, Guimarães M, Silva C et al (1997) Supression of bladder hyperreflexia by intravesical resiniferatoxin. Lancet 350:640–641

    Article  PubMed  CAS  Google Scholar 

  46. Lazzeri M, Beneforti P, Turini D (1997) Urodynamic effects of intravesical resiniferatoxin in humans: preliminary results in stable and unstable detrusor. J Urol 158:2093–2096

    Article  PubMed  CAS  Google Scholar 

  47. Kuo HC, Liu HT, Yang WC (2006) Therapeutic effect of multiple resiniferatoxin intravesical instillations in patients with refractory detrusor overactivity: a randomized, double-blind, placebo controlled study. J Urol 176:641–645

    Article  PubMed  CAS  Google Scholar 

  48. Silva C, Rio ME, Cruz F (2000) Desensitization of bladder sensory fibers by intravesical resiniferatoxin, a capsaicin analog: long-term results for the treatment of detrusor hyperreflexia. Eur Urol 38:444–452

    Article  PubMed  CAS  Google Scholar 

  49. Apostolidis A, Popat R, Yiangou Y 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 174:977–982, discussion 982–983

    Article  PubMed  CAS  Google Scholar 

  50. Silva C, Silva J, Castro H et al (2007) Bladder sensory desensitization decreases urinary urgency. BMC Urol 11:7–9

    Google Scholar 

  51. Silva C, Ribeiro MJ, Cruz F (2002) The effect of intravesical resiniferatoxin in patients with idiopathic detrusor instability suggests that involuntary detrusor contractions are triggered by C-fiber input. J Urol 168:575–579

    Article  PubMed  CAS  Google Scholar 

  52. Kuo HC (2003) Effectiveness of intravesical resiniferatoxin for anticholinergic treatment refractory detrusor overactivity due to nonspinal cord lesions. J Urol 170:835–839

    Article  PubMed  Google Scholar 

  53. Dinis P, Silva J, Ribeiro MJ et al (2004) Bladder C-fiber desensitization induces a long-lasting improvement of BPH-associated storage LUTS: a pilot study. Eur Urol 46:88–93

    Article  PubMed  Google Scholar 

  54. Lazzeri M, Beneforti M, Spinelli A et al (2000) Intravesical resiniferatoxin for the treatment of hypersensitive disorder: a randomized placebo controlled study. J Urol 164:676–679

    Article  PubMed  CAS  Google Scholar 

  55. Apostolidis A, Gonzales GE, Fowler CJ (2006) Effect of intravesical resiniferatoxin (RTX) on lower urinary tract symptoms, urodynamic parameters, and quality of life of patients with urodynamic increased bladder sensation. Eur Urol 50:1299–1305

    Article  PubMed  CAS  Google Scholar 

  56. Mukerji G, Yiangou Y, Agarwal SK et al (2006) Transient receptor potential vanilloid receptor subtype 1 in painful bladder syndrome and its correlation with pain. J Urol 176:797–801

    Article  PubMed  CAS  Google Scholar 

  57. Chen TY, Corcos J, Camel M et al (2005) Prospective, randomized, double-blind study of safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC). Int Urogynecol J Pelvic Floor Dysfunct 16:293–297

    Article  PubMed  CAS  Google Scholar 

  58. Peng CH, Kuo HC (2007) Multiple intravesical instillations of low-dose resiniferatoxin in the treatment of refractory interstitial cystitis. Urol Int 78:78–81

    Article  PubMed  CAS  Google Scholar 

  59. Payne CK, Mosbaugh PG, Forrest JB et al (2005) Intravesical resiniferatoxin for the treatment of interstitial cystitis: a randomized, double-blind, placebo controlled trial. J Urol 173:1590–1594

    Article  PubMed  CAS  Google Scholar 

  60. Liu L, Mansfield KJ, Kristiana I et al (2007) The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder. Neurourol Urodyn 26:433–438

    Article  PubMed  CAS  Google Scholar 

  61. Caudle RM, Karai L, Mena N et al (2003) Resiniferatoxin-induced loss of plasma membrane in vanilloid receptor expressing cells. Neurotoxicology 24:895–908

    Article  PubMed  CAS  Google Scholar 

  62. Lee SY, Hong Y, Oh U (2004) Decreased pain sensitivity of capsaicin-treated rats results from decreased VR1 expression. Arch Pharm Res 27:1154–1160

    Article  PubMed  CAS  Google Scholar 

  63. Santos-Silva A, Charrua A, Cruz CD et al (2012) Rat detrusor overactivity induced by chronic spinalization can be abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist. Auton Neurosci 166:35–38

    Article  PubMed  CAS  Google Scholar 

  64. Brady CM, Apostolidis AN, Harper M 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. BJU Int 93:770–776

    Article  PubMed  CAS  Google Scholar 

  65. Xu X, Wang P, Zou X et al (2009) Increases in transient receptor potential vanilloid-1 mRNA and protein in primary afferent neurons stimulated by protein kinase C and their possible role in neurogenic inflammation. J Neurosci Res 87:482–494

    Article  PubMed  CAS  Google Scholar 

  66. Ji RR, Samad TA, Jin SX et al (2002) p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36:57–68

    Article  PubMed  CAS  Google Scholar 

  67. Xue Q, Jong B, Chen T et al (2007) Transcription of rat TRPV1 utilizes a dual promoter system that is positively regulated by nerve growth factor. J Neurochem 101:212–222

    Article  PubMed  CAS  Google Scholar 

  68. Okragly AJ, Niles AL, Saban R, Schmidt D, Hoffman RL, Warner TF, Moon TD, Uehling DT, Haak-Frendscho M (1999) Elevated tryptase, nerve growth factor, neurotrophin-3 and glial cell line-derived neurotrophic factor levels in the urine of interstitial cystitis and bladder cancer patients. J Urol 161:438–441

    Article  PubMed  CAS  Google Scholar 

  69. Kim JC, Park EY, Seo SI, Park YH, Hwang TK (2006) Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder. J Urol 151:1773–1776

    Article  CAS  Google Scholar 

  70. Giannantoni A, Di Stasi SM, Nardicchi V, Zucchi A, Macchioni L, Bini V, Goracci G, Porena M (2006) Botulinum-A toxin injections into the detrusor muscle decrease nerve growth factor bladder tissue levels in patients with neurogenic detrusor overactivity. J Urol 151:2341–2344

    Article  CAS  Google Scholar 

  71. Liu HT, Chancellor MB, Kuo HC (2008) Urinary nerve growth factor level could be a biomarker in the differential diagnosis of mixed urinary incontinence in women. BJU Int 102:1440–1444

    PubMed  Google Scholar 

  72. Liu HT, Chancellor MB, Kuo HC (2009) Urinary nerve growth factor levels are elevated in patients with detrusor overactivity and decreased in responders to detrusor botulinum toxin-A injection. Eur Urol 56:700–706

    Article  PubMed  CAS  Google Scholar 

  73. Stein AT, Ufret-Vincenty CA, Hua L et al (2006) Phosphoinositide 3-kinase binds to TRPV1 and mediates NGF-stimulated TRPV1 trafficking to the plasma membrane. J Gen Physiol 128:509–522

    Article  PubMed  CAS  Google Scholar 

  74. Schumacher MA, Moff I, Sudanagunta SP et al (2000) Molecular cloning of an N-terminal splice variant of the capsaicin receptor. Loss of N-terminal domain suggests functional divergence among capsaicin receptor subtypes. J Biol Chem 275:2756–2762

    Article  PubMed  CAS  Google Scholar 

  75. Lu G, Henderson D, Liu L, Reinhart PH, Simon SA (2005) TRPV1b, a functional human vanilloid receptor splice variant. Mol Pharmacol 67(4):1119–1127

    Article  PubMed  CAS  Google Scholar 

  76. Charrua A, Reguenga C, Paule CC et al (2008) Cystitis is associated with TRPV1b-downregulation in rat dorsal root ganglia. Neuroreport 19:1469–1472

    Article  PubMed  CAS  Google Scholar 

  77. Zygmunt PM, Petersson J, Andersson DA et al (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452–457

    Article  PubMed  CAS  Google Scholar 

  78. Huang SM, Bisogno T, Trevisani M et al (2002) An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc Natl Acad Sci USA 99:8400–8405

    Article  PubMed  CAS  Google Scholar 

  79. Chu CJ, Huang SM, De Petrocellis L et al (2003) N-oleoyldopamine, a novel endogenous capsaicin-like lipid that produces hyperalgesia. J Biol Chem 278:13633–13639

    Article  PubMed  CAS  Google Scholar 

  80. Hwang SW, Cho H, Kwak J et al (2000) Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances. Proc Natl Acad Sci USA 97:6155–6160

    Article  PubMed  CAS  Google Scholar 

  81. Dinis P, Charrua A, Avelino A 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 24:11253–11263

    Article  PubMed  CAS  Google Scholar 

  82. Lee SY, Lee JH, Kang KK et al (2005) Sensitization of vanilloid receptor involves an increase in the phosphorylated form of the channel. Arch Pharm Res 28:405–412

    Article  PubMed  CAS  Google Scholar 

  83. Sculptoreanu A, de Groat WC, Buffington CA et al (2005) Protein kinase C contributes to abnormal capsaicin responses in DRG neurons from cats with feline interstitial cystitis. Neurosci Lett 381:42–46

    Article  PubMed  CAS  Google Scholar 

  84. Cortright DN, Szallasi A (2004) Biochemical pharmacology of the vanilloid receptor TRPV1. An update. Eur J Biochem 271:1814–1819

    Article  PubMed  CAS  Google Scholar 

  85. Li M, Sun Y, Simard JM et al (2011) Increased transient receptor potential vanilloid type 1 (TRPV1) signaling in idiopathic overactive bladder urothelial cells. Neurourol Urodyn 30:606–611

    Article  PubMed  CAS  Google Scholar 

  86. Apostolidis A, Brady CM, Yiangou Y et al (2005) Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin. Urology 65:400–405

    Article  PubMed  Google Scholar 

  87. Szallasi A, Cruz F, Geppetti P (2006) TRPV1: a therapeutic target for novel analgesic drugs? Trends Mol Med 12:545–554

    Article  PubMed  CAS  Google Scholar 

  88. Jancsó-Gabor A, Szolcsanyi J, Jancso N (1970) Irreversible impairment of thermoregulation induced by capsaicin and similar pungent substances in rats and guinea-pigs. J Physiol 206:495–507

    PubMed  Google Scholar 

  89. Swanson DM, Dubin AE, Shah C et al (2005) Identification and biological evaluation of 4-(3-trifluoromethylpyridin-2-yl)piperazine-1-carboxylic acid (5-trifluoromethylpyridin-2-yl)amide, a high affinity TRPV1 (VR1) vanilloid receptor antagonist. J Med Chem 48:1857–1872

    Article  PubMed  CAS  Google Scholar 

  90. Romanovsky AA (2007) Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system. Am J Physiol Regul Integr Comp Physiol 292:R37–R46

    Article  PubMed  CAS  Google Scholar 

  91. Steiner AA, Turek VF, Almeida MC et al (2007) Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors. J Neurosci 27:7459–7468

    Article  PubMed  CAS  Google Scholar 

  92. Gavva NR (2008) Body-temperature maintenance as the predominant function of the vanilloid receptor TRPV1. Trends Pharmacol Sci 29:550–557

    Article  PubMed  CAS  Google Scholar 

  93. Gavva NR, Treanor JJ, Garami A et al (2008) Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain 136:202–210

    Article  PubMed  CAS  Google Scholar 

  94. Wong GY, Gavva NR (2008) Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: recent advances and setbacks. Brain Res Rev 60:267–277

    Article  PubMed  CAS  Google Scholar 

  95. Szallasi A, Cortright DN, Blum CA et al (2007) The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept. Nat Rev Drug Discov 6:357–372

    Article  PubMed  CAS  Google Scholar 

  96. Huang W, Rubinstein J, Prieto AR et al (2010) Enhanced postmyocardial infarction fibrosis via stimulation of the transforming growth factor-beta-Smad2 signaling pathway: role of transient receptor potential vanilloid type 1 channels. J Hypertens 28:367–376

    Article  PubMed  CAS  Google Scholar 

  97. Everaerts W, Zhen X, Ghosh D et al (2010) Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis. Proc Natl Acad Sci USA 107:19084–19089

    Article  PubMed  CAS  Google Scholar 

  98. Miyamoto T, Mochizuki T, Zakohji H et al (2009) The expression of transient receptor potential (TRP) V4, A1, and V1 in the human bladder mucosa of normal and bladder outlet obstruction – a novel mechanism in the obstruction-induced bladder overactivity. Neurourol Urodyn 28:12

    Google Scholar 

  99. Lemos AE, Ferreira J, André E et al (2006) Contractile mechanisms coupled to TRPA1 receptor activation in rat urinary bladder. Biochem Pharmacol 72:104–114

    Article  CAS  Google Scholar 

  100. Andrade EL, Forner S, Bento AF et al (2011) TRPA1 receptor modulation attenuates bladder overactivity induced by spinal cord injury. Am J Physiol Renal Physiol 300:F1223–F1234

    Article  PubMed  CAS  Google Scholar 

  101. Chen J, Joshi SK, DiDomenico S et al (2011) Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation. Pain 152:1165–1172

    Article  PubMed  CAS  Google Scholar 

  102. Du S, Akari I, Kobayashi H et al (2008) Differential expression profile of cold (TRPA1) and cool (TRPM8) receptors in human urogenital organs. Urology 72:450–455

    Article  PubMed  Google Scholar 

  103. Hayashi T, Kondo T, Ishimatsu M et al (2011) Function and expression pattern of TRPM8 in bladder afferent neurons associated with bladder outlet obstruction in rats. Auton Neurosci 164:27–33

    Article  PubMed  CAS  Google Scholar 

  104. Jung J, Shin JS, Lee SY et al (2004) Phosphorylation of vanilloid receptor 1 by Ca2+/calmodulin-dependent kinase II regulates its vanilloid binding. J Biol Chem 279:7048–7054

    Article  PubMed  CAS  Google Scholar 

  105. Amadesi S, Cottrell GS, Divino L et al (2006) Protease-activated receptor 2 sensitizes TRPV1 by protein kinase Cepsilon- and A-dependent mechanisms in rats and mice. J Physiol 575:555–571

    Article  PubMed  CAS  Google Scholar 

  106. Amadesi S, Nie J, Vergnolle N et al (2004) Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. J Neurosci 24:4300–4312

    Article  PubMed  CAS  Google Scholar 

  107. Ohta T, Ikemi Y, Murakami M et al (2006) Potentiation of transient receptor potential V1 functions by the activation of metabotropic 5-HT receptors in rat primary sensory neurons. J Physiol 576:809–822

    Article  PubMed  CAS  Google Scholar 

  108. Dattilio A, Vizzard MA (2005) Up-regulation of protease activated receptors in bladder after cyclophosphamide induced cystitis and colocalization with capsaicin receptor (VR1) in bladder nerve fibers. J Urol 173:635–639

    Article  PubMed  CAS  Google Scholar 

  109. Carlton SM, Du J, Zhou S (2009) Group II metabotropic glutamate receptor activation on peripheral nociceptors modulates TRPV1 function. Brain Res 1248:86–95

    Article  PubMed  CAS  Google Scholar 

  110. Vetter I, Wyse BD, Monteith GR et al (2006) The mu opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway. Mol Pain 2:22–37

    Article  PubMed  CAS  Google Scholar 

  111. Vetter I, Cheng W, Peiris M et al (2008) Rapid, opioid-sensitive mechanisms involved in transient receptor potential vanilloid 1 sensitization. J Biol Chem 283:19540–19550

    Article  PubMed  CAS  Google Scholar 

  112. Yoshiyama M, de Groat WC (2007) Role of spinal metabotropic glutamate receptors in regulation of lower urinary tract function in the decerebrate unanesthetized rat. Neurosci Lett 420:18–22

    Article  PubMed  CAS  Google Scholar 

  113. Andersson KE (2002) Bladder activation: afferent mechanisms. Urology 59:43–50

    Article  PubMed  Google Scholar 

  114. Kumar V, Chapple CR, Rosario D et al (2010) In vitro release of adenosine triphosphate from the urothelium of human bladders with detrusor overactivity, both neurogenic and idiopathic. Eur Urol 57:1087–1092

    Article  PubMed  Google Scholar 

  115. Ford AP, Cockayne DA (2011) ATP and P2X purinoceptors in urinary tract disorders. Handb Exp Pharmacol 202:485–526

    Article  PubMed  CAS  Google Scholar 

  116. Sun Y, Keay S, de Deyne PG et al (2001) Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis. J Urol 166:1951–1956

    Article  PubMed  CAS  Google Scholar 

  117. Ford APDW, Gever JR, Nunn PA et al (2006) Purinoceptors as therapeutic targets for lower urinary tract dysfunction. Br J Pharmacol 147:S132–S143

    Article  PubMed  CAS  Google Scholar 

  118. Sadananda P, Shang F, Liu L et al (2009) Release of ATP from rat urinary bladder mucosa: role of acid, vanilloids and stretch. Br J Pharmacol 158:1655–1662

    Article  PubMed  CAS  Google Scholar 

  119. Elneil S, Skepper JN, Kidd EJ et al (2001) Distribution of P2X(1) and P2X(3) receptors in the rat and human urinary bladder. Pharmacology 63:120–128

    Article  PubMed  CAS  Google Scholar 

  120. Sun Y, Chai TC (2004) Up-regulation of P2X3 receptor during stretch of bladder urothelial cells from patients with interstitial cystitis. J Urol 171:448–452

    Article  PubMed  CAS  Google Scholar 

  121. Tempest HV, Dixon AK, Turner WH et al (2004) P2X and P2X receptor expression in human bladder urothelium and changes in interstitial cystitis. BJU Int 93:1344–1348

    Article  PubMed  CAS  Google Scholar 

  122. Walczak JS, Price TJ, Cervero F (2009) Cannabinoid CB1 receptors are expressed in the mouse urinary bladder and their activation modulates afferent bladder activity. Neuroscience 159:1154–1163

    Article  PubMed  CAS  Google Scholar 

  123. Walczak JS, Cervero F (2011) Local activation of cannabinoid CB1 receptors in the urinary bladder reduces the inflammation-induced sensitization of bladder afferents. Mol Pain 7:31

    Article  PubMed  CAS  Google Scholar 

  124. Premkumar LS, Ahern GP (2000) Induction of vanilloid receptor channel activity by protein kinase C. Nature 408:985–990

    Article  PubMed  CAS  Google Scholar 

  125. Vellani V, Mapplebeck S, Moriondo A et al (2001) Protein kinase C activation potentiates gating of the vanilloid receptor VR1 by capsaicin, protons, heat and anandamide. J Physiol 534:813–825

    Article  PubMed  CAS  Google Scholar 

  126. Sugiura T, Tominaga M, Katsuya H et al (2002) Bradykinin lowers the threshold temperature for heat activation of vanilloid receptor 1. J Neurophysiol 88:544–548

    PubMed  CAS  Google Scholar 

  127. Carr MJ, Lollarik M, Meeker SN et al (2003) A role for TRPV1 in bradykinin-induced excitation of vagal airway afferent nerve terminals. J Pharmacol Exp Ther 304:1275–1279

    Article  PubMed  CAS  Google Scholar 

  128. Tang HB, Inoue A, Oshita K et al (2004) Sensitization of vanilloid receptor 1 induced by bradykinin via the activation of second messenger signaling cascades in rat primary afferent neurons. Eur J Pharmacol 498:37–43

    Article  PubMed  CAS  Google Scholar 

  129. Mizumura K, Sugiur T, Koda H et al (2005) Pain and bradykinin receptors-sensory transduction mechanism in the nociceptor terminals and expression change of bradykinin receptors in inflamed condition. Nihon Shinkei Seishin Yakurigaku Zasshi 25:33–38

    PubMed  CAS  Google Scholar 

  130. Shin J, Cho H, Hwang SW et al (2002) Bradykinin-12-lipoxygenase-VR1 signalling pathway for inflammatory hyperalgesia. Proc Natl Acad Sci USA 99:10150–10155

    Article  PubMed  CAS  Google Scholar 

  131. Ferreira J, da Silva GL, Calixto JB (2004) Contribution of vanilloid receptors to the overt nociception induced by B2 kinin receptor activation in mice. Br J Pharmacol 141: 787–794

    Article  PubMed  CAS  Google Scholar 

  132. Wang Y, Wang DH (2011) Protective Effect of TRPV1 against Renal Fibrosis via Inhibition of TGF-β/Smad Signaling in DOCA-Salt Hypertension. Mol Med 17:1204–1212

    PubMed  Google Scholar 

  133. Wang Y, Wang DH (2009) Aggravated renal inflammatory responses in TRPV1 gene knockout mice subjected to DOCA-salt hypertension. Am J Physiol Renal Physiol 297:F1550–F1559

    Article  PubMed  CAS  Google Scholar 

  134. Ueda K, Tsuji F, Hirata T et al (2009) Preventive effect of SA13353 [1-[2-(1-adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea], a novel transient receptor potential vanilloid 1 agonist, on ischemia/reperfusion-induced renal injury in rats. J Pharmacol Exp Ther 329:202–209

    Article  PubMed  CAS  Google Scholar 

  135. Xie C, Sachs JR, Wang DH (2008) Interdependent regulation of afferent renal nerve activity and renal function: role of transient receptor potential vanilloid type 1, neurokinin 1, and calcitonin gene-related peptide receptors. J Pharmacol Exp Ther 325:751–757

    Article  PubMed  CAS  Google Scholar 

  136. Zhu Y, Wang Y, Wang DH (2005) Diuresis and natriuresis caused by activation of VR1-positive sensory nerves in renal pelvis of rats. Hypertension 46:992–997

    Article  PubMed  CAS  Google Scholar 

  137. Li J, Wang DH (2008) Increased GFR and renal excretory function by activation of TRPV1 in the isolated perfused kidney. Pharmacol Res 57:239–246

    Article  PubMed  CAS  Google Scholar 

  138. Kawamata T, Ji W, Yamamoto J et al (2008) Contribution of transient receptor potential vanilloid subfamily 1 to endothelin-1-induced thermal hyperalgesia. Neuroscience 154:1067–1076

    Article  PubMed  CAS  Google Scholar 

  139. Zhu Y, Wang DH (2008) Segmental regulation of sodium and water excretion by TRPV1 activation in the kidney. J Cardiovasc Pharmacol 51:437–442

    Article  PubMed  CAS  Google Scholar 

  140. Gao F, Sui D, Garavito RM et al (2009) Salt intake augments hypotensive effects of transient receptor potential vanilloid 4: functional significance and implication. Hypertension 53:228–235

    Article  PubMed  CAS  Google Scholar 

  141. Gao F, Wang DH (2010) Impairment in function and expression of transient receptor potential vanilloid type 4 in Dahl salt-sensitive rats: significance and mechanism. Hypertension 55:1018–1025

    Article  PubMed  CAS  Google Scholar 

  142. Xie C, Wang DH (2010) Effects of a high-salt diet on TRPV-1-dependent renal nerve activity in Dahl salt-sensitive rats. Am J Nephrol 32:194–200

    Article  PubMed  CAS  Google Scholar 

  143. Xie C, Wang DH (2009) Ablation of transient receptor potential vanilloid 1 abolishes endothelin-induced increases in afferent renal nerve activity: mechanisms and functional significance. Hypertension 54:1298–1305

    Article  PubMed  CAS  Google Scholar 

  144. Zhu Y, Xie C, Wang DH (2007) TRPV1-mediated diuresis and natriuresis induced by hypertonic saline perfusion of the renal pelvis. Am J Nephrol 27:530–537

    Article  PubMed  CAS  Google Scholar 

  145. Feng NH, Lee HH, Shiang JC et al (2008) Transient receptor potential vanilloid type 1 channels act as mechanoreceptors and cause substance P release and sensory activation in rat kidneys. Am J Physiol Renal Physiol 294:F316–F325

    Article  PubMed  CAS  Google Scholar 

  146. Li J, Wang DH (2006) Differential mechanisms mediating depressor and diuretic effects of anandamide. J Hypertens 24:2271–2276

    Article  PubMed  CAS  Google Scholar 

  147. Sanchez JF, Krause JE, Cortright DN (2001) The distribution and regulation of vanilloid receptor VR1 and VR1 5′ splice variant RNA expression in rat. Neuroscience 107(3):373–381

    Article  PubMed  CAS  Google Scholar 

  148. Vos MH, Neelands TR, McDonald HA et al (2006) TRPV1b overexpression negatively regulates TRPV1 responsiveness to capsaicin, heat and low pH in HEK293 cells. J Neurochem 99:1088–1102

    Article  PubMed  CAS  Google Scholar 

  149. Wang C, Hu HZ, Colton CK et al (2004) An alternative splicing product of the murine trpv1 gene dominant negatively modulates the activity of TRPV1 channels. J Biol Chem 279:37423–37430

    Article  PubMed  CAS  Google Scholar 

  150. Tian W, Fu Y, Wang DH et al (2006) Regulation of TRPV1 by a novel renally expressed rat TRPV1 splice variant. Am J Physiol Renal Physiol 290:F117–F126

    Article  PubMed  CAS  Google Scholar 

  151. Eilers H, Lee SY, Hau CW et al (2007) The rat vanilloid receptor splice variant VR.5′sv blocks TRPV1 activation. Neuroreport 18:969–973

    Article  PubMed  CAS  Google Scholar 

  152. Tian W, Salanova M, Xu H et al (2004) Renal expression of osmotically responsive cation channel TRPV4 is restricted to water-impermeant nephron segments. Am J Physiol Renal Physiol 287:F17–F24

    Article  PubMed  Google Scholar 

  153. Cohen DM (2005) TRPV4 and the mammalian kidney. Pflugers Arch 451:168–175

    Article  PubMed  CAS  Google Scholar 

  154. Delany NS, Hurle M, Facer P et al (2001) Identification and characterization of a novel human vanilloid receptor-like protein, VRL-2. Physiol Genomics 4:165–174

    PubMed  CAS  Google Scholar 

  155. Taniguchi J, Tsuruoka S, Mizuno A et al (2006) TRPV4 as a flow sensor in flow-dependent K+ secretion from the cortical collecting duct. Am J Physiol Renal Physiol 292:F667–F673

    Article  PubMed  CAS  Google Scholar 

  156. Haas M, Forbush B 3rd (1998) The Na-K-Cl cotransporters. J Bioenerg Biomembr 30:161–172

    Article  PubMed  CAS  Google Scholar 

  157. Kim JA, Yang H, Hwang I et al (2011) Expression patterns and potential action of the calcium transport genes trpv5, trpv6, ncx1 and pmca1b in the canine duodenum, kidney and uterus. In Vivo 25:773–780

    PubMed  CAS  Google Scholar 

  158. Hwang I, Jung EM, Yang H et al (2011) Tissue-specific expression of the calcium transporter genes TRPV5, TRPV6, NCX1, and PMCA1b in the duodenum, kidney and heart of Equus caballus. J Vet Med Sci 73(11):1437–1444

    Article  PubMed  CAS  Google Scholar 

  159. Peng JB, Brown EM, Hedigerb MA (2001) Structural conservation of the genes encoding CaT1, CaT2, and related cation channels. Genomics 76:99–109

    Article  PubMed  CAS  Google Scholar 

  160. Peng JB, Chen XZ, Berger UV et al (2000) A rat kidney-specific calcium transporter in the distal nephron. J Biol Chem 275:28186–28194

    PubMed  CAS  Google Scholar 

  161. Hoenderop JGJ, Van der Kemp AW, Hartog A et al (1999) Molecular identification of the apical epithelial Ca2+ channel in 1, 25-vitamin D3 responsive epithelia. J Biol Chem 274:8375–8378

    Article  PubMed  CAS  Google Scholar 

  162. Hoenderop JG, Vennekens R, Müller D et al (2001) Function and expression of the epithelial Ca(2+) channel family: comparison of mammalian ECaC1 and 2. J Physiol 537:747–761

    Article  PubMed  CAS  Google Scholar 

  163. Mensenkamp AR, Hoenderop JG, Bindels RJ (2007) TRPV5, the gateway to Ca2+ homeostasis. Handb Exp Pharmacol 179:207–220

    Article  PubMed  CAS  Google Scholar 

  164. Goel M, Sinkins WG, Zuo CD et al (2006) Identification and localization of TRPC channels in the rat kidney. Am J Physiol Renal Physiol 290:F1241–F1252

    Article  PubMed  CAS  Google Scholar 

  165. Ilatovskaya DV, Levchenko V, Ryan RP et al (2011) NSAIDs acutely inhibit TRPC channels in freshly isolated rat glomeruli. Biochem Biophys Res Commun 408:242–247

    Article  PubMed  CAS  Google Scholar 

  166. Wang X, Pluznick JL, Wei P et al (2004) TRPC4 forms store-operated Ca2+ channels in mouse mesangial cells. Am J Physiol Cell Physiol 287:C357–C364

    Article  PubMed  CAS  Google Scholar 

  167. Graham S, Ding M, Sours-Brothers S et al (2007) Downregulation of TRPC6 protein expression by high glucose, a possible mechanism for the impaired Ca2+ signaling in glomerular mesangial cells in diabetes. Am J Physiol Renal Physiol 293:F1381–F1390

    Article  PubMed  CAS  Google Scholar 

  168. Sours S, Du J, Chu S et al (2006) Expression of canonical transient receptor potential (TRPC) proteins in human glomerular mesangial cells. Am J Physiol Renal Physiol 290:F1507–F1515

    Article  PubMed  CAS  Google Scholar 

  169. Sours-Brothers S, Ding M, Graham S et al (2009) Interaction between TRPC1/TRPC4 assembly and STIM1 contributes to store-operated Ca2+ entry in mesangial cells. Exp Biol Med (Maywood) 234:673–682

    Article  CAS  Google Scholar 

  170. Raychowdhury MK, McLaughlin M, Ramos AJ et al (2005) Characterization of single channel currents from primary cilia of renal epithelial cells. J Biol Chem 280:34718–34722

    Article  PubMed  CAS  Google Scholar 

  171. Yoder BK, Hou X, Guay-Woodford LM (2002) The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J Am Soc Nephrol 13:2508–2516

    Article  PubMed  CAS  Google Scholar 

  172. Luo Y, Vassilev PM, Li X et al (2003) Native polycystin 2 functions as a plasma membrane Ca2+-permeable cation channel in renal epithelia. Mol Cell Biol 23:2600–2607

    Article  PubMed  CAS  Google Scholar 

  173. Goel M, Sinkins WG, Zuo CD et al (2007) Vasopressin-induced membrane trafficking of TRPC3 and AQP2 channels in cells of the rat renal collecting duct. Am J Physiol Renal Physiol 293:F1476–F1488

    Article  PubMed  CAS  Google Scholar 

  174. Bandyopadhyay BC, Swaim WD, Liu X et al (2005) Apical localization of a functional TRPC3/TRPC6-Ca2+-signaling complex in polarized epithelial cells. Role in apical Ca2+ influx. J Biol Chem 280:12908–12916

    Article  PubMed  CAS  Google Scholar 

  175. Salomonsson M, Braunstein TH, Holstein-Rathlou NH et al (2010) Na+-independent, nifedipine-resistant rat afferent arteriolar Ca2+ responses to noradrenaline: possible role of TRPC channels. Acta Physiol (Oxf) 200:265–278

    Article  CAS  Google Scholar 

  176. Lee-Kwon W, Wade JB, Zhang Z et al (2005) Expression of TRPC4 channel protein that interacts with NHERF-2 in rat descending vasa recta. Am J Physiol Cell Physiol 288:C942–C949

    Article  PubMed  CAS  Google Scholar 

  177. Muallem S, Moe OW (2007) When EGF is offside, magnesium is wasted. J Clin Invest 117:2086–2089

    Article  PubMed  CAS  Google Scholar 

  178. Voets T, Nilius B, Hoefs S et al (2004) TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption. J Biol Chem 279:19–25

    Article  PubMed  CAS  Google Scholar 

  179. Maggi CA, Santicioli P, Manzini S et al (1989) Functional studies on the cholinergic and sympathetic innervation of the rat proximal urethra: effect of pelvic ganglionectomy or experimental diabetes. J Auton Pharmacol 9:231–241

    Article  PubMed  CAS  Google Scholar 

  180. Andersson PO, Malmgren A, Uvelius B (1990) Functional responses of different muscle types of the female rat urethra in vitro. Acta Physiol Scand 140:365–372

    Article  PubMed  CAS  Google Scholar 

  181. Maggi CA, Giuliani S, Santicioli P et al (1987) Visceromotor responses to calcitonin gene-related peptide (CGRP) in the rat lower urinary tract: evidence for a transmitter role in the capsaicin-sensitive nerves of the ureter. Eur J Pharmacol 143:73–82

    Article  PubMed  CAS  Google Scholar 

  182. Nishizawa S, Igawa Y, Okada N et al (1997) Capsaicin-induced nitric-oxide-dependent relaxation in isolated dog urethra. Eur J Pharmacol 335:211–219

    Article  PubMed  CAS  Google Scholar 

  183. Conte B, Maggi CA, Giachetti A et al (1993) Intraurethral capsaicin produces reflex ­activation of the striated urethral sphincter in urethane-anesthetized male rats. J Urol 150:1271–1277

    PubMed  CAS  Google Scholar 

  184. Maggi CA, Santicioli P, Abelli L et al (1987) Regional differences in the effects of capsaicin and tachykinins on motor activity and vascular permeability of the rat lower urinary tract. Naunyn Schmiedebergs Arch Pharmacol 335:636–645

    Article  PubMed  CAS  Google Scholar 

  185. Peng HY, Huang PC, Liao JM et al (2008) Estrous cycle variation of TRPV1-mediated cross-organ sensitization between uterus and NMDA-dependent pelvic-urethra reflex activity. Am J Physiol Endocrinol Metab 295:E559–E568

    Article  PubMed  CAS  Google Scholar 

  186. Peng HY, Chang HM, Lee SD et al (2008) TRPV1 mediates the uterine capsaicin-induced NMDA NR2B-dependent cross-organ reflex sensitization in anesthetized rats. Am J Physiol Renal Physiol 295:F1324–F1335

    Article  PubMed  CAS  Google Scholar 

  187. Gratzke C, Streng T, Waldkirch E et al (2009) Transient receptor potential A1 (TRPA1) activity in the human urethra – evidence for a functional role for TRPA1 in the outflow region. Eur Urol 55:696–704

    Article  PubMed  CAS  Google Scholar 

  188. Weinhold P, Gratzke C, Streng T et al (2010) TRPA1 receptor induced relaxation of the human urethra involves TRPV1 and cannabinoid receptor mediated signals, and cyclooxygenase activation. J Urol 183:2070–2076

    Article  PubMed  CAS  Google Scholar 

  189. Xu ZP, Gao WC, Wang HP et al (2009) Expression of transient receptor potential subfamily mRNAs in rat testes. Nan Fang Yi Ke Da Xue Xue Bao 29:519–520

    PubMed  CAS  Google Scholar 

  190. Mizrak SC, van Dissel-Emiliani FM (2008) Transient receptor potential vanilloid receptor-1 confers heat resistance to male germ cells. Fertil Steril 90:1290–1293

    Article  PubMed  CAS  Google Scholar 

  191. Li S, Wang X, Ye H et al (2010) Distribution profiles of transient receptor potential melastatin- and vanilloid-related channels in rat spermatogenic cells and sperm. Mol Biol Rep 37:1287–1293

    Article  PubMed  CAS  Google Scholar 

  192. Martínez-López P, Treviño CL, de la Vega-Beltrán JL et al (2011) TRPM8 in mouse sperm detects temperature changes and may influence the acrosome reaction. J Cell Physiol 226:1620–1631

    Article  PubMed  CAS  Google Scholar 

  193. Auzanneau C, Norez C, Antigny F et al (2008) Transient receptor potential vanilloid 1 (TRPV1) channels in cultured rat Sertoli cells regulate an acid sensing chloride channel. Biochem Pharmacol 75:476–483

    Article  PubMed  CAS  Google Scholar 

  194. Mizrak SC, Gadella BM, Erdost H et al (2008) Spermatogonial stem cell sensitivity to capsaicin: an in vitro study. Reprod Biol Endocrinol 6:52

    Article  PubMed  CAS  Google Scholar 

  195. Boldyrev OI, Sotkis HV, IeM K et al (2009) Expression of the cold receptor TRPM8 in the smooth muscles of the seminal ejaculatory ducts in rats. Fiziol Zh 55:17–27

    PubMed  CAS  Google Scholar 

  196. Filippov IB, Vladymyrova IA, IeM K (2009) Modulation of the smooth muscle contractions of the rat vas deferens by TRPM8 channel agonist menthol. Fiziol Zh 55:30–40

    PubMed  CAS  Google Scholar 

  197. Maggi CA, Giuliani S, Santicioli P et al (1987) Capsaicin-induced inhibition of motility of the rat isolated vas deferens: do multiple neuropeptides mediate the visceromotor effects of capsaicin? J Auton Pharmacol 7:243–255

    Article  PubMed  CAS  Google Scholar 

  198. Ellis JL, Burnstock G (1989) Modulation of neurotransmission in the guinea-pig vas deferens by capsaicin: involvement of calcitonin gene-related peptide and substance P. Br J Pharmacol 98:707–713

    Article  PubMed  CAS  Google Scholar 

  199. Wardle KA, Furey G, Sanger GJ (1996) Pharmacological characterization of the vanilloid receptor in the rat isolated vas deferens. J Pharm Pharmacol 48:285–291

    Article  PubMed  CAS  Google Scholar 

  200. Filippelli A, Falciani M, Piucci B (1999) Endothelin-1 affects capsaicin-evoked release of neuropeptides from rat vas deferens. Eur J Pharmacol 364:183–191

    Article  PubMed  CAS  Google Scholar 

  201. Ross RA, Gibson TM, Brockie HC et al (2001) Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens. Br J Pharmacol 132:631–640

    Article  PubMed  CAS  Google Scholar 

  202. Thomas A, Pertwee RG (2006) The bioassay of cannabinoids using the mouse isolated vas deferens. Methods Mol Med 123:191–207

    PubMed  CAS  Google Scholar 

  203. Sheykhzade M, Gupta S, Sørensen T et al (2011) Characterization of capsaicin induced responses in mice vas deferens: evidence of CGRP uptake. Eur J Pharmacol 667:375–382

    Article  PubMed  CAS  Google Scholar 

  204. Wang HP, Pu XY, Wang XH (2007) Distribution profiles of transient receptor potential melastatin-related and vanilloid-related channels in prostatic tissue in rat. Asian J Androl 9:634–640

    Article  PubMed  CAS  Google Scholar 

  205. Dinis P, Charrua A, Avelino A et al (2005) The distribution of sensory fibres immunoreactive for the TRPV1 (capsaicin) receptor in the human prostate. Eur Urol 48:162–167

    Article  PubMed  Google Scholar 

  206. Van der Aa F, Roskams T, Blyweert W et al (2003) Interstitial cells in the human prostate: a new therapeutic target? Prostate 56:250–255

    Article  PubMed  Google Scholar 

  207. Gratzke C, Weinhold P, Reich O et al (2009) Transient receptor potential A1 and cannabinoid receptor activity in human normal and hyperplastic prostate: relation to nerves and interstitial cells. Eur Urol 57:902–910

    Article  PubMed  CAS  Google Scholar 

  208. Bidaux G, Roudbaraki M, Merle C et al (2005) Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement. Endocr Relat Cancer 12:367–382

    Article  PubMed  CAS  Google Scholar 

  209. Kondrats’kyĭ AP, Sotkis HV, Boldyriev OI (2007) Functional identification of the TRPM8 cold receptor in rat prostate epithelial cells. Fiziol Zh 53:3–13

    PubMed  Google Scholar 

  210. Tsavaler L, Shapero MH, Morkowski S et al (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 61:3760–3769

    PubMed  CAS  Google Scholar 

  211. Bidaux G, Flourakis M, Thebault S et al (2007) Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function. J Clin Invest 117:1647–1657

    Article  PubMed  CAS  Google Scholar 

  212. Lazzeri M, Barbanti G, Beneforti P et al (1994) Intraurethrally infused capsaicin induces penile erection in humans. Scand J Urol Nephrol 28:409–412

    Article  PubMed  CAS  Google Scholar 

  213. Bai VU, Murthy S, Chinnakannu K et al (2010) Androgen regulated TRPM8 expression: a potential mRNA marker for metastatic prostate cancer detection in body fluids. Int J Oncol 36:443–450

    PubMed  CAS  Google Scholar 

  214. Vanden AF, Zholos A, Bidaux G et al (2006) Ca2+-independent phospholipase A2-dependent gating of TRPM8 by lysophospholipids. J Biol Chem 281:40174–40182

    Article  CAS  Google Scholar 

  215. Zhang L, Barritt GJ (2004) Evidence that TRPM8 is an androgen-dependent Ca2+ channel required for the survival of prostate cancer cells. Cancer Res 64:8365–8373

    Article  PubMed  CAS  Google Scholar 

  216. Kim SH, Nam JH, Park EJ et al (2008) Menthol regulates TRPM8-independent processes in PC-3 prostate cancer cells. Biochim Biophys Acta 1792:33–38

    PubMed  Google Scholar 

  217. Kim SH, Kim SY, Park EJ et al (2011) Icilin induces G1 arrest through activating JNK and p38 kinase in a TRPM8-independent manner. Biochem Biophys Res Commun 406:30–35

    Article  PubMed  Google Scholar 

  218. Yang Z, Wang X, Zhu G et al (2012) Effect of surgical castration on expression of TRPM8 in urogenital tract of male rats. Mol Biol Rep 39(4):4797–4802

    Article  PubMed  CAS  Google Scholar 

  219. Teilmann SC, Byskov AG, Pedersen PA et al (2005) Localization of transient receptor potential ion channels in primary and motile cilia of the female murine reproductive organs. Mol Reprod Dev 71:444–452

    Article  PubMed  CAS  Google Scholar 

  220. Andrade YN, Fernandes J, Vázquez E et al (2005) TRPV4 channel is involved in the coupling of fluid viscosity changes to epithelial ciliary activity. J Cell Biol 168:869–874

    Article  PubMed  CAS  Google Scholar 

  221. Dörr J, Fecher-Trost C (2011) TRP channels in female reproductive organs and placenta. Adv Exp Med Biol 704:909–928

    Article  PubMed  CAS  Google Scholar 

  222. Meseguer V, Karashima Y, Talavera K et al (2008) Transient receptor potential channels in sensory neurons are targets of the antimycotic agent clotrimazole. J Neurosci 28(3):576–586

    Article  PubMed  CAS  Google Scholar 

  223. Kalogris C, Caprodossi S, Amantini C et al (2010) Expression of transient receptor potential vanilloid-1 (TRPV1) in urothelial cancers of human bladder: relation to clinicopathological and molecular parameters. Histopathology 57:744–752

    Article  PubMed  Google Scholar 

  224. Yamada T, Ueda T, Shibata Y et al (2010) TRPV2 activation induces apoptotic cell death in human T24 bladder cancer cells: a potential therapeutic target for bladder cancer. Urology 76:509.e1–509.e7

    Article  Google Scholar 

  225. Ziglioli F, Frattini A, Maestroni U et al (2009) Vanilloid-mediated apoptosis in prostate cancer cells through a TRPV-1 dependent and a TRPV-1-independent mechanism. Acta Biomed 80:13–20

    PubMed  CAS  Google Scholar 

  226. Sánchez AM, Sánchez MG, Malagarie-Cazenave S et al (2006) Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin. Apoptosis 11:89–99

    Article  PubMed  CAS  Google Scholar 

  227. Malagarie-Cazenave S, Olea-Herrero N, Vara D et al (2011) The vanilloid capsaicin induces IL-6 secretion in prostate PC-3 cancer cells. Cytokine 54:330–337

    Article  PubMed  CAS  Google Scholar 

  228. Sánchez AM, Malagarie-Cazenave S, Olea N et al (2007) Apoptosis induced by capsaicin in prostate PC-3 cells involves ceramide ­accumulation, neutral sphingomyelinase, and JNK activation. Apoptosis 12:2013–2024

    Article  PubMed  CAS  Google Scholar 

  229. Mori A, Lehmann S, O’Kelly J et al (2006) Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells. Cancer Res 66:3222–3229

    Article  PubMed  CAS  Google Scholar 

  230. Sánchez AM, Martínez-Botas J, Malagarie-Cazenave S et al (2008) Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: a microarray study. Biochem Biophys Res Commun 372:785–791

    Article  PubMed  CAS  Google Scholar 

  231. Jankovic B, Loblaw DA, Nam R (2010) Capsaicin may slow PSA doubling time: case report and literature review. Can Urol Assoc J 4:E9–E11

    PubMed  Google Scholar 

  232. Huang JK, Cheng HH, Huang CJ et al (2005) Effect of capsazepine on cytosolic Ca(2+) levels and proliferation of human prostate cancer cells. Toxicol In Vitro 20:567–574

    Article  PubMed  CAS  Google Scholar 

  233. Gkika D, Flourakis M, Lemonnier L et al (2010) PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression. Oncogene 29:4611–4616

    Article  PubMed  CAS  Google Scholar 

  234. Gkika D, Prevarskaya N (2011) TRP channels in prostate cancer: the good, the bad and the ugly? Asian J Androl 13(5):673–676

    Article  PubMed  Google Scholar 

  235. Yang ZH, Wang XH, Wang HP et al (2009) Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells. Asian J Androl 11:157–165

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was partially supported by INComb FP7 HEALTH Project 223234. AC has been supported by SFRH/BPD/68716/2101 Fellowship from Fundação para a Ciência e a Tecnologia.

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Authors and Affiliations

  1. Department of Urology, Hospital São João, Porto, Portugal

    Ana Charrua & Francisco Cruz

  2. IBMC – Instituto de Biologia Molecular e Celular, Department of Experimental Biology, Faculty of Medicine and Faculty of Nutrition & Food Sciences, Universidade do Porto, Porto, Portugal

    Ana Charrua

  3. IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal

    Francisco Cruz

Authors
  1. Ana Charrua
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  2. Francisco Cruz
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Correspondence to Francisco Cruz .

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Editors and Affiliations

  1. , Transfusion Services, Monmouth Medical Center, Second Avenue 300, Long Branch, 07740, New Jersey, USA

    Arpad Szallasi

  2. Medical and Health Science Center, Department of Physiology, University of Debrecen, Nagyerdei Krt. 98, Debrecen, 4032, Hungary

    Tamás Bíró

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© 2012 Springer Science+Business Media, LLC

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Charrua, A., Cruz, F. (2012). TRP Channels in the Genitourinary Tract. In: Szallasi, A., Bíró, T. (eds) TRP Channels in Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-077-9_19

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  • DOI: https://doi.org/10.1007/978-1-62703-077-9_19

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-076-2

  • Online ISBN: 978-1-62703-077-9

  • eBook Packages: Springer Protocols

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