The role of the transient receptor potential (TRP) superfamily of cation-selective channels in the management of the overactive bladder
Karl-Erik Andersson
Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA, *Department of Urology, Ludwig-Maximilians University Hospital, Munich, Germany, † Department of Clinical and Experimental Pharmacology, Lund University, ‡ Department of Clinical Pharmacology, Linköping University, Sweden, § Urological Research Institute, Department of Urology, San Raffaele University, Milan, Italy
Search for more papers by this authorChristian Gratzke
Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA, *Department of Urology, Ludwig-Maximilians University Hospital, Munich, Germany, † Department of Clinical and Experimental Pharmacology, Lund University, ‡ Department of Clinical Pharmacology, Linköping University, Sweden, § Urological Research Institute, Department of Urology, San Raffaele University, Milan, Italy
Search for more papers by this authorPetter Hedlund
Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA, *Department of Urology, Ludwig-Maximilians University Hospital, Munich, Germany, † Department of Clinical and Experimental Pharmacology, Lund University, ‡ Department of Clinical Pharmacology, Linköping University, Sweden, § Urological Research Institute, Department of Urology, San Raffaele University, Milan, Italy
Search for more papers by this authorKarl-Erik Andersson
Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA, *Department of Urology, Ludwig-Maximilians University Hospital, Munich, Germany, † Department of Clinical and Experimental Pharmacology, Lund University, ‡ Department of Clinical Pharmacology, Linköping University, Sweden, § Urological Research Institute, Department of Urology, San Raffaele University, Milan, Italy
Search for more papers by this authorChristian Gratzke
Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA, *Department of Urology, Ludwig-Maximilians University Hospital, Munich, Germany, † Department of Clinical and Experimental Pharmacology, Lund University, ‡ Department of Clinical Pharmacology, Linköping University, Sweden, § Urological Research Institute, Department of Urology, San Raffaele University, Milan, Italy
Search for more papers by this authorPetter Hedlund
Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston Salem, NC, USA, *Department of Urology, Ludwig-Maximilians University Hospital, Munich, Germany, † Department of Clinical and Experimental Pharmacology, Lund University, ‡ Department of Clinical Pharmacology, Linköping University, Sweden, § Urological Research Institute, Department of Urology, San Raffaele University, Milan, Italy
Search for more papers by this authorAbstract
• The pathophysiology of lower urinary tract symptoms (LUTS), detrusor overactivity (DO), and the overactive bladder (OAB) syndrome is multifactorial and remains poorly understood.
• The transient receptor potential (TRP) channel superfamily has been shown to be involved in nociception and mechanosensory transduction in various organ systems, and studies of the LUT have indicated that several TRP channels, including TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1, are expressed in the bladder, and may act as sensors of stretch and/or chemical irritation.
• However, the roles of these individual channels for normal LUT function and in LUTS/DO/OAB, have not been established.
• TRPV1 is the channel best investigated. It is widely distributed in LUT structures, but despite extensive information on morphology and function in animal models, the role of this channel in normal human bladder function is still controversial. Conversely, its role in the pathophysiology and treatment of particularly neurogenic DO is well established.
• TRPV1 is co-expressed with TRPA1, and TRPA1 is known to be present on capsaicin-sensitive primary sensory neurones. Activation of this channel can induce DO in animal models.
• TRPV4 is a Ca2+-permeable stretch-activated cation channel, involved in stretch-induced ATP release, and TRPV4-deficient mice exhibit abnormal frequencies of voiding and non-voiding contractions in cystometric experiments.
• TRPM8 is a cool receptor expressed in the urothelium and suburothelial sensory fibres. It has been implicated in the bladder-cooling reflex and in idiopathic DO.
• The occurrence of other members of the TRP superfamily in the LUT has been reported, but information on their effects on LUT functions is scarce. There seem to be several links between activation of different members of the TRP superfamily and LUTS/DO/OAB, and further exploration of the involvement of these channels in LUT function, normally and in dysfunction, may be rewarding.
REFERENCES
- 1 Andersson KE, Arner A. Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev 2004; 84: 935–86
- 2 Andersson KE, Wein AJ. Pharmacology of the lower urinary tract: basis for current and future treatments of urinary incontinence. Pharmacol Rev 2004; 56: 581–631
- 3 De Groat WC. Integrative control of the lower urinary tract: preclinical perspective. Br J Pharmacol 2006; 147 (Suppl. 2): S25–40
- 4 Yoshida M, Masunaga K, Nagata T, Yono M, Homma Y. The forefront for novel therapeutic agents based on the pathophysiology of lower urinary tract dysfunction: pathophysiology and pharmacotherapy of overactive bladder. J Pharmacol Sci 2010; 112: 128–34
- 5 Yoshimura N, Kaiho Y, Miyazato M et al. Therapeutic receptor targets for lower urinary tract dysfunction. Naunyn Schmiedebergs Arch Pharmacol 2008; 377: 437–48
- 6 De Groat WC, Yoshimura N. Afferent nerve regulation of bladder function in health and disease. Handb Exp Pharmacol 2009; 194: 91–138
- 7 Birder LA. Urothelial signaling. Auton Neurosci 2010; 153: 33–40
- 8 Birder LA, Wolf-Johnston AS, Chib MK, Buffington CA, Roppolo JR, Hanna-Mitchell AT. Beyond neurons: involvement of urothelial and glial cells in bladder function. Neurourol Urodyn 2010; 29: 88–96
- 9 Kanai A, Andersson KE. Bladder afferent signaling: recent findings. J Urol 2010; 183: 1288–95
- 10 Andersson KE. Detrusor myocyte activity and afferent signaling. Neurourol Urodyn 2010; 29: 97–106
- 11 Araki I, Du S, Kobayashi H et al. Roles of mechanosensitive ion channels in bladder sensory transduction and overactive bladder. Int J Urol 2008; 15: 681–7
- 12 Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation channels in disease. Physiol Rev 2007; 87: 165–217
- 13 Birnbaumer L. The TRPC class of ion channels: a critical review of their roles in slow, sustained increases in intracellular Ca(2+) concentrations. Annu Rev Pharmacol Toxicol 2009; 49: 395–426
- 14 Eid SR, Cortight DN. Transient receptor potential channels on sensory nerves. Handb Exp Pharmacol 2009; 194: 261–81
- 15 Everaerts W, Gevaert T, Nilius B, De Ridder D. On the origin of bladder sensing: Tr(i)ps in urology. Neurourol Urodyn 2008; 27: 264–73
- 16 De Groat WC. A neurologic basis for the overactive bladder. Urology 1997; 50 (Suppl.): 36–56
- 17 Gillespie JI. The autonomous bladder: a view of the origin of bladder overactivity and sensory urge. BJU Int 2004; 93: 478–83
- 18 Gillespie JI. A developing view of the origins of urgency: the importance of animal models. BJU Int 2005; 96 (Suppl. 1): 22–8
- 19 Drake MJ, Mills IW, Gillespie JI. Model of peripheral autonomous modules and a myovesical plexus in normal and overactive bladder function. Lancet 2001; 358: 401–3
- 20 Zagorodnyuk VP, Costa M, Brookes SJ. Major classes of sensory neurons to the urinary bladder. Auton Neurosci 2006; 126–127: 390–7
- 21 Zagorodnyuk VP, Gibbins IL, Costa M, Brookes SJ, Gregory SJ. Properties of the major classes of mechanoreceptors in the guinea pig bladder. J Physiol 2007; 585: 147–63
- 22 Andersson KE. Storage and voiding symptoms: pathophysiologic aspects. Urology 2003; 62 (Suppl. 2): 3–10
- 23 Roosen A, Chapple CR, Dmochowski RR et al. A refocus on the bladder as the originator of storage lower urinary tract symptoms: a systematic review of the latest literature. Eur Urol 2009; 56: 810–20
- 24 Hashitani H, Brading AF, Suzuki H. Correlation between spontaneous electrical, calcium and mechanical activity in detrusor smooth muscle of the guinea-pig bladder. Br J Pharmacol 2004; 141: 183–93
- 25 Gillespie JI, Van Koeveringe GA, De Wachter SG, De Vente J. On the origins of the sensory output from the bladder: the concept of afferent noise. BJU Int 2009; 103: 1324–33
- 26 Thorneloe KS, Sulpizio AC, Lin Z et al. 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 2008; 326: 432–42
- 27 Andrade EL, Ferreira J, André E, Calixto JB. Contractile mechanisms coupled to TRPA1 receptor activation in rat urinary bladder. Biochem Pharmacol 2006; 72: 104–14
- 28 Streng T, Axelsson HE, Hedlund P et al. Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol 2008; 53: 391–9
- 29 Wu C, Sui GP, Fry CH. Purinergic regulation of guinea pig suburothelial myofibroblasts. J Physiol 2004; 559: 231–43
- 30 Fry CH, Sui GP, Kanai AJ, Wu C. The function of suburothelial myofibroblasts in the bladder. Neurourol Urodyn 2007; 26 (Suppl.): 914–9
- 31 Ikeda Y, Kanai A. Urotheliogenic modulation of intrinsic activity in spinal cord-transected rat bladders: role of mucosal muscarinic receptors. Am J Physiol Renal Physiol 2008; 295: F454–61
- 32 Sui GP, Wu C, Roosen A, Ikeda Y, Kanai AJ, Fry CH. Modulation of bladder myofibroblast activity: implications for bladder function. Am J Physiol Renal Physiol 2008; 295: F688–97
- 33 Birder L, Kullmann FA, Lee H et al. 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 2007; 323: 227–35
- 34 Andersson KE. Bladder activation: afferent mechanisms. Urology 2002; 59 (Suppl. 1): 43–50
- 35 De Groat WC. The urothelium in overactive bladder: passive bystander or active participant? Urology 2004; 64 (Suppl. 1): 7–11
- 36 Birder LA, De Groat WC. Mechanisms of disease: involvement of the urothelium in bladder dysfunction. Nat Clin Pract Urol 2007; 4: 46–54
- 37 Ferguson DR, Kennedy I, Burton TJ. ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes – a possible sensory mechanism? J Physiol 1997; 505: 503–11
- 38 Fovaeus M, Fujiwara M, Hogestatt ED, Persson K, Andersson KE. A non-nitrergic smooth muscle relaxant factor released from rat urinary bladder by muscarinic receptor stimulation. J Urol 1999; 161: 649–53
- 39 Hawthorn MH, Chapple CR, Cock M, Chess-Williams R. Urothelium-derived inhibitory factor(s) influences on detrusor muscle contractility in vitro. Br J Pharmacol 2000; 129: 416–9
- 40 Templeman L, Chapple CR, Chess-Williams R. Urothelium derived inhibitory factor and cross-talk among receptors in the trigone of the bladder of the pig. J Urol 2002; 167: 742–5
- 41 Fowler CJ, Griffiths D, De Groat WC. The neural control of micturition. Nat Rev Neurosci 2008; 9: 453–66
- 42 De Groat WC, Kawatani M, Hisamitsu T et al. Mechanisms underlying the recovery of urinary bladder function following spinal cord injury. J Auton Nerv Syst 1990; 30: S71–7
- 43 Geppetti P, Nassini R, Materazzi S, Benemei S. The concept of neurogenic inflammation. BJU Int 2008; 101 (Suppl. 3): 2–6
- 44 Yamada T, Ugawa S, Ueda T, Ishida Y, Kajita K, Shimada S. Differential localizations of the transient receptor potential channels TRPV4 and TRPV1 in the mouse urinary bladder. J Histochem Cytochem 2009; 57: 277–87
- 45 Nilius B. TRP channels in disease. Biochim Biophys Acta 2007; 1772: 805–12
- 46 Birder LA, Nakamura Y, Kiss S et al. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 2002; 5: 856–60
- 47 Story GM, Peier AM, Reeve AJ et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 2003; 112: 819–65
- 48 Gevaert T, Vriens J, Segal A et al. Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J Clin Invest 2007; 117: 3453–62
- 49 Stein RJ, Santos S, Nagatomi J et al. Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol 2004; 172: 1175–8
- 50 Tsukimi Y, Mizuyachi K, Yamasaki T, Niki T, Hayashi F. Cold response of the bladder in guinea pig: involvement of transient receptor potential channel, TRPM8. Urology 2005; 65: 406–10
- 51 Du S, Araki I, Kobayashi H, Zakoji H, Sawada N, Takeda M. Differential expression profile of cold (TRPA1) and cool (TRPM8) receptors in human urogenital organs. Urology 2008; 72: 450–5
- 52 Mukerji G, Yiangou Y, Corcoran SL et al. Cool and menthol receptor TRPM8 in human urinary bladder disorders and clinical correlations. BMC Urol 2006; 6: 6
- 53 Tominaga M, Caterina MJ, Malmberg AB et al. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998; 21: 531–43
- 54 Tominaga M, Tominaga T. Structure and function of TRPV1. Pflugers Arch 2005; 451: 143–50
- 55 Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997; 389: 816–24
- 56 Vennekens R, Owsianik G, Nilius B. Vanilloid transient receptor potential cation channels: an overview. Curr Pharm Des 2008; 14: 18–31
- 57 Avelino A, Cruz F. TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications. Naunyn Schmiedebergs Arch Pharmacol 2006; 373: 287–99
- 58 Szallasi A, Goso C, Blumberg PM, Manzini S. Competitive inhibition by capsazepine of [3H]resiniferatoxin binding to central (spinal cord and dorsal root ganglia) and peripheral (urinary bladder and airways) vanilloid (capsaicin) receptors in the rat. J Pharmacol Exp Ther 1993; 267: 728–33
- 59 Ost D, Roskams T, Van Der Aa F, De Ridder D. Topography of the vanilloid receptor in the human bladder: more than just the nerve fibers. J Urol 2002; 168: 293–7
- 60 Avelino A, Cruz C, Nagy I, Cruz F. Vanilloid receptor 1 expression in the rat urinary tract. Neuroscience 2002; 109: 787–98
- 61 Van der Aa F, Roskams T, Blyweert W, De Ridder D. Interstitial cells in the human prostate: a new therapeutic target? Prostate 2003; 56: 250–5
- 62 Mochizuki T, Sokabe T, Araki I et al. The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures. J Biol Chem 2009; 284: 21257–64
- 63 Everaerts W, Vriens J, Owsianik G et al. Functional characterization of transient receptor potential channels in mouse urothelial cells. Am J Physiol Renal Physiol 2010; 298: F692–701
- 64 Lazzeri M, Vannucchi MG, Zardo C et al. Immunohistochemical evidence of vanilloid receptor 1 in normal human urinary bladder. Eur Urol 2004; 46: 792–8
- 65 Lazzeri M, Vannucchi MG, Spinelli M et al. Transient receptor potential vanilloid type 1 (TRPV1) expression changes from normal urothelium to transitional cell carcinoma of human bladder. Eur Urol 2005; 48: 691–8
- 66 Apostolidis A, Brady CM, Yiangou Y, Davis J, Fowler CJ, Anand P. Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin. Urology 2005; 65: 400–5
- 67 Apostolidis A, Popat R, Yiangou Y et al. Decreased sensory receptors P2X3 and TRPV1 in suburothelial nerve fibers following intradetrusor injections of botulinum toxin for human detrusor overactivity. J Urol 2005; 174: 977– 83
- 68 Dinis P, Charrua A, Avelino A et al. The distribution of sensory fibers immunoreactive for the TRPV1 (capsaicin) receptor in the human prostate. Eur Urol 2005; 48: 162–7
- 69 Brady CM, Apostolidis AN, Harper M et al. 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 2004; 93: 770–6
- 70 Daly D, Rong W, Chess-Williams R, Chapple C, Grundy D. Bladder afferent sensitivity in wild-type and TRPV1 knockout mice. J Physiol 2007; 583: 663–74
- 71 Cruz F, Dinis P. Resiniferatoxin and botulinum toxin type A for treatment of lower urinary tract symptoms. Neurourol Urodyn 2007; 26 (Suppl.): 920–7
- 72 MacDonald R, Monga M, Fink HA, Wilt TJ. Neurotoxin treatments for urinary incontinence in subjects with spinal cord injury or multiple sclerosis: a systematic review of effectiveness and adverse effects. J Spinal Cord Med 2008; 31: 157–65
- 73 Andersson KE, Chapple CR, Cardozo L et al. Pharmacological treatment of overactive bladder: report from the International Consultation on Incontinence. Curr Opin Urol 2009; 19: 380–94
- 74 Maggi CA, Barbanti G, Santicioli P et al. Cystometric evidence that capsaicin-sensitive nerves modulate the afferent branch of micturition reflex in humans. J Urol 1989; 142: 150–4
- 75 Liu L, Mansfield KJ, Kristiana I, Vaux KJ, Millard RJ, Burcher E. The molecular basis of urgency: regional difference of vanilloid receptor expression in the human urinary bladder. Neurourol Urodyn 2007; 26: 433–9
- 76 Hindmarsh JR, Gosling PT, Deane AM. Bladder instability. Is the primary defect in the urethra? Br J Urol 1983; 55: 648–51
- 77 Low JA, Armstrong JB, Mauger GM. The unstable urethra in the female. Obstet Gynecol 1989; 74: 69–74
- 78 Farrell SA, Tynski G. The effect of urethral pressure variation on detrusor activity in women. Int Urogynecol J Pelvic Floor Dysfunct 1996; 7: 87–93
- 79 McLennan MT, Melick C, Bent AE. Urethral instability: clinical and urodynamic characteristics. Neurourol Urodyn 2001; 20: 653–60
- 80 Suzuki M, Watanabe Y, Oyama Y et al. Localization of mechanosensitive channel TRPV4 in mouse skin. Neurosci Lett 2003; 353: 189–92
- 81 Robain G, Combrisson H, Mazières L. Bladder response to urethral flow in the awake ewe. Neurourol Urodyn 2001; 20: 641–9
- 82 Combrisson H, Allix S, Robain G. Influence of temperature on urethra to bladder micturition reflex in the awake ewe. Neurourol Urodyn 2007; 26: 290–5
- 83 Jordt SE, Bautista DM, Chuang HH et al. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 2004; 427: 260–5
- 84 Bautista DM, Siemens J, Glazer JM et al. The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 2007; 448: 204–8
- 85 Zurborg S, Yurgionas B, Jira JA, Caspani O, Heppenstall PA. Direct activation of the ion channel TRPA1 by Ca2+. Nat Neurosci 2007; 10: 277–9
- 86 Hinman A, Chuang HH, Bautista DM, Julius D. TRP channel activation by reversible covalent modification. Proc Natl Acad Sci USA 2006; 103: 19564– 8
- 87 Macpherson LJ, Dubin AE, Evans MJ et al. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 2007; 445: 541–5
- 88 Kindt KS, Viswanath V, MacPherson L et al. Caenorhabditis elegans TRPA-1 functions in mechanosensation. Nat Neurosci 2007; 10: 568–77
- 89 Bautista DM, Jordt SE, Nikai T et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 2006; 124: 1269–82
- 90 Kwan KY, Allchorne AJ, Vollrath MA et al. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 2006; 50: 277–89
- 91 Nagata K, Duggan A, Kumar G, García-Añoveros J. Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing. J Neurosci 2005; 25: 4052–61
- 92 Gratzke C, Streng T, Waldkirch E et al. Transient receptor potential A1 (TRPA1) activity in the human urethra – evidence for a functional role for TRPA1 in the outflow region. Eur Urol 2009; 55: 696–704
- 93 Weinhold P, Gratzke C, Streng T, Stief C, Andersson KE, Hedlund P. TRPA1 receptor induced relaxation of the human urethra involves TRPV1 and cannabinoid receptor mediated signals, and cyclooxygenase activation. J Urol 2010; 183: 2070–6
- 94 Bautista DM, Movahed P, Hinman A et al. Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci USA 2005; 102: 12248–52
- 95 Karashima Y, Damann N, Prenen J et al. Bimodal action of menthol on the transient receptor potential channel TRPA1. J Neurosci 2007; 27: 9874–84
- 96 Du S, Araki I, Yoshiyama M, Nomura T, Takeda M. Transient receptor potential channel A1 involved in sensory transduction of rat urinary bladder through C-fiber pathway. Urology 2007; 70: 826–31
- 97 McNamara CR, Mandel-Brehm J, Bautista DM et al. TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci USA 2007; 104: 13525–30
- 98 Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R. Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay. Br J Pharmacol 2004; 141: 737–45
- 99 Lashinger ES, Steiginga MS, Hieble JP et al. AMTB, a TRPM8 channel blocker: evidence in rats for activity in overactive bladder and painful bladder syndrome. Am J Physiol Renal Physiol 2008; 295: F803–10
- 100 Hayashi T, Kondo T, Ishimatsu M et al. Expression of the TRPM8-immunoreactivity in dorsal root ganglion neurons innervating the rat urinary bladder. Neurosci Res 2009; 65: 245–51
- 101 Chai TC, Gray ML, Steers WD. The incidence of a positive ice water test in bladder outlet obstructed patients: evidence for bladder neural plasticity. J Urol 1998; 160: 34–8
- 102 Mukerji G, Waters J, Chessell IP, Bountra C, Agarwal SK, Anand P. Pain during ice water test distinguishes clinical bladder hypersensitivity from overactivity disorders. BMC Urol 2006; 6: 31
- 103 Nomoto Y, Yoshida A, Ikeda S et al. Effect of menthol on detrusor smooth-muscle contraction and the micturition reflex in rats. Urology 2008; 72: 701– 5
- 104 Zhang L, Barritt GJ. TRPM8 in prostate cancer cells: a potential diagnostic and prognostic marker with a secretory function? Endocr Relat Cancer 2006; 13: 27–38
- 105 Imamura T, Ishizuka O, Aizawa N et al. Cold environmental stress induces detrusor overactivity via resiniferatoxin-sensitive nerves in conscious rats. Neurourol Urodyn 2008; 27: 348–52
- 106 Chen Z, Ishizuka O, Imamura T et al. Stimulation of skin menthol receptors stimulates detrusor activity in conscious rats. Neurourol Urodyn 2010; 29: 506–11
- 107 Neeper MP, Liu Y, Hutchinson TL, Wang Y, Flores CM, Qin N. Activation properties of heterologously expressed mammalian TRPV2: evidence for species dependence. J Biol Chem 2007; 282: 15894–902
- 108 Muraki K, Iwata Y, Katanosaka Y et al. TRPV2 is a component of osmotically sensitive cation channels in murine aortic myocytes. Circ Res 2003; 93: 829–38
- 109 Caprodossi S, Lucciarini R, Amantini C et al. 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 2008; 54: 612–20
- 110 Cefalu JS, Guillon MA, Burbach LR et al. Selective pharmacological blockade of the TRPV1 receptor suppresses sensory reflexes of the rodent bladder. J Urol 2009; 182: 776–85
- 111 Charrua A, Cruz CD, Narayanan S et al. GRC-6211, a new oral specific TRPV1 antagonist, decreases bladder overactivity and noxious bladder input in cystitis animal models. J Urol 2009; 181: 379–86