Skip to main content
SpringerLink
Log in

Sensor and Transducer Function of the Urothelium: Pathological Implications

  • Reference work entry
  • First Online:
Handbook of Neurourology

  • 431 Accesses

Abstract

A classic physical barrier, the urothelium has been recognized as a new type of sensory structure. The urothelium can sense bladder distension and transduce the mechanical signal into chemical signal by releasing the sensory mediator ATP. ATP in turn acts on the P2X receptors of the afferent fibers to generate nerve impulses. The suburothelial cell network amplifies the urothelial signal. The system can also respond to a variety of noxious stimuli, contributing to pathological processes. An extensive collection of nociceptive and mechanoreceptive receptors and ion channels enables the urothelium to receive multiple sensory inputs. The pathological importance is evidenced by functional and structural lesions of the urothelium in human bladder pathologies and their experimental models. The distinct ion channel and receptor profiles make the urothelium a promising drug target for more selective pharmacological interventions for the treatment of bladder disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 999.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 999.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. B.F. Martin, Cell replacement and differentiation in transitional epithelium: a histological and autoradiographic study of the guinea-pig bladder and ureter. J. Anat. 112, 433–455 (1972)

    CAS  PubMed  PubMed Central  Google Scholar 

  2. X.R. Wu, X.P. Kong, A. Pellicer, G. Kreibich, T.T. Sun, Uroplakins in urothelial biology, function, and disease. Kidney Int. 75, 1153–1165 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. M.L. Zeidel, Low permeabilities of apical membranes of barrier epithelia: what makes watertight membranes watertight? Am. J. Phys. 271, F243–F245 (1996)

    CAS  Google Scholar 

  4. H.O. Negrete, J.P. Lavelle, J. Berg, S.A. Lewis, M.L. Zeidel, Permeability properties of the intact mammalian bladder epithelium. Am. J. Phys. 271, F886–F894 (1996)

    CAS  Google Scholar 

  5. D. Kikeri, A. Sun, M.L. Zeidel, S.C. Hebert, Cell membranes impermeable to NH3. Nature 339, 478–480 (1989)

    Article  CAS  PubMed  Google Scholar 

  6. R.M. Hicks, The permeability of rat transitional epithelium. Kertinization and the barrier to water. J. Cell Biol. 28, 21–31 (1966)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. R.M. Hicks, B. Ketterer, R.C. Warren, The ultrastructure and chemistry of the luminal plasma membrane of the mammalian urinary bladder: a structure with low permeability to water and ions. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 268, 23–38 (1974)

    CAS  Google Scholar 

  8. C. Clausen, S.A. Lewis, J.M. Diamond, Impedance analysis of a tight epithelium using a distributed resistance model. Biophys. J. 26, 291–317 (1979)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. S. Peter, The junctional connections between the cells of the urinary bladder in the rat. Cell Tissue Res. 187, 439–448 (1978)

    Article  CAS  PubMed  Google Scholar 

  10. J.P. Lavelle, G. Apodaca, S.A. Meyers, W.G. Ruiz, M.L. Zeidel, Disruption of guinea pig urinary bladder permeability barrier in noninfectious cystitis. Am. J. Phys. 274, F205–F214 (1998)

    CAS  Google Scholar 

  11. S. Keay, J.W. Warren, C.O. Zhang, L.M. Tu, D.A. Gordon, K.E. Whitmore, Antiproliferative activity is present in bladder but not renal pelvic urine from interstitial cystitis patients. J. Urol. 162, 1487–1489 (1999)

    Article  CAS  PubMed  Google Scholar 

  12. S. Keay, C.O. Zhang, T. Chai, J. Warren, K. Koch, D. Grkovic, H. Colville, R. Alexander, Antiproliferative factor, heparin-binding epidermal growth factor-like growth factor, and epidermal growth factor in men with interstitial cystitis versus chronic pelvic pain syndrome. Urology 63, 22–26 (2004)

    Article  PubMed  Google Scholar 

  13. L.A. Birder, A. Wolf-Johnston, C.A. Buffington, J.R. Roppolo, W.C. de Groat, A.J. Kanai, Altered inducible nitric oxide synthase expression and nitric oxide production in the bladder of cats with feline interstitial cystitis. J. Urol. 173, 625–629 (2005)

    Article  CAS  PubMed  Google Scholar 

  14. P. Veranic, K. Jezernik, The response of junctional complexes to induced desquamation in mouse bladder urothelium. Biol. Cell. 92, 105–113 (2000)

    Article  CAS  PubMed  Google Scholar 

  15. A.T. Hanna-Mitchell, A. Wolf-Johnston, J.R. Roppolo, T.C. Buffington, L.A. Birder, Corticotropin-releasing factor family peptide signaling in feline bladder urothelial cells. J. Endocrinol. 222, 113–121 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. P. Veranic, K. Jezernik, Succession of events in desquamation of superficial urothelial cells as a response to stress induced by prolonged constant illumination. Tissue Cell 33, 280–285 (2001)

    Article  CAS  PubMed  Google Scholar 

  17. J.H. Shie, H.T. Liu, H.C. Kuo, Increased cell apoptosis of urothelium mediated by inflammation in interstitial cystitis/painful bladder syndrome. Urology 79, 484–413 (2012)

    Article  Google Scholar 

  18. G. Apodaca, S. Kiss, W. Ruiz, S. Meyers, M. Zeidel, L. Birder, Disruption of bladder epithelium barrier function after spinal cord injury. Am. J. Physiol. Renal Physiol. 284, F966–F976 (2003)

    Article  CAS  PubMed  Google Scholar 

  19. D.R. Ferguson, I. Kennedy, T.J. Burton, ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes–a possible sensory mechanism? J. Physiol. 505(Pt 2), 503–511 (1997)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. W. Rong, K.M. Spyer, G. Burnstock, Activation and sensitisation of low and high threshold afferent fibres mediated by P2X receptors in the mouse urinary bladder. J. Physiol. 541, 591–600 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. D.A. Cockayne, S.G. Hamilton, Q.M. Zhu, P.M. Dunn, Y. Zhong, S. Novakovic, A.B. Malmberg, G. Cain, A. Berson, L. Kassotakis, L. Hedley, W.G. Lachnit, G. Burnstock, S.B. McMahon, A.P. Ford, Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 407, 1011–1015 (2000)

    Article  CAS  PubMed  Google Scholar 

  22. M. Vlaskovska, L. Kasakov, W. Rong, P. Bodin, M. Bardini, D.A. Cockayne, A.P. Ford, G. Burnstock, P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J. Neurosci. 21, 5670–5677 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. G. Gabella, C. Davis, Distribution of afferent axons in the bladder of rats. J. Neurocytol. 27, 141–155 (1998)

    Article  CAS  PubMed  Google Scholar 

  24. Y. Wakabayashi, T. Tomoyoshi, M. Fujimiya, R. Arai, T. Maeda, Substance P-containing axon terminals in the mucosa of the human urinary bladder: pre-embedding immunohistochemistry using cryostat sections for electron microscopy. Histochemistry 100, 401–407 (1993)

    Article  CAS  PubMed  Google Scholar 

  25. A. Avelino, F. Cruz, TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications. Naunyn Schmiedeberg’s Arch. Pharmacol. 373, 287–299 (2006)

    Article  CAS  Google Scholar 

  26. L.A. Birder, A.J. Kanai, W.C. de Groat, S. Kiss, M.L. Nealen, N.E. Burke, K.E. Dineley, S. Watkins, I.J. Reynolds, M.J. Caterina, Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc. Natl. Acad. Sci. U. S. A. 98, 13396–13401 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. R.A. Davidson, K.D. McCloskey, Morphology and localization of interstitial cells in the guinea pig bladder: structural relationships with smooth muscle and neurons. J. Urol. 173, 1385–1390 (2005)

    Article  PubMed  Google Scholar 

  28. M.J. Drake, C.H. Fry, B. Eyden, Structural characterization of myofibroblasts in the bladder. BJU Int. 97, 29–32 (2006)

    Article  PubMed  Google Scholar 

  29. M. Lagou, J. de Vente, T.B. Kirkwood, P. Hedlund, K.E. Andersson, J.I. Gillespie, M.J. Drake, Location of interstitial cells and neurotransmitters in the mouse bladder. BJU Int. 97, 1332–1337 (2006)

    Article  CAS  PubMed  Google Scholar 

  30. J.I. Gillespie, I.M. Markerink-Van, J. De Vente, Interstitial cells and cholinergic signalling in the outer muscle layers of the guinea-pig bladder. BJU Int. 97, 379–385 (2006)

    Article  CAS  PubMed  Google Scholar 

  31. P.J. Smet, J. Jonavicius, V.R. Marshall, J. De Vente, Distribution of nitric oxide synthase-immunoreactive nerves and identification of the cellular targets of nitric oxide in guinea-pig and human urinary bladder by cGMP immunohistochemistry. Neuroscience 71, 337–348 (1996)

    Article  CAS  PubMed  Google Scholar 

  32. G.P. Sui, S. Rothery, E. Dupont, C.H. Fry, N.J. Severs, Gap junctions and connexin expression in human suburothelial interstitial cells. BJU Int. 90, 118–129 (2002)

    Article  CAS  PubMed  Google Scholar 

  33. K.D. McCloskey, A.M. Gurney, Kit positive cells in the guinea pig bladder. J. Urol. 168, 832–836 (2002)

    Article  PubMed  Google Scholar 

  34. C. Wu, G.P. Sui, C.H. Fry, Purinergic regulation of guinea pig suburothelial myofibroblasts. J. Physiol. 559, 231–243 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. G.P. Sui, C. Wu, C.H. Fry, Electrical characteristics of suburothelial cells isolated from the human bladder. J. Urol. 171, 938–943 (2004)

    Article  CAS  PubMed  Google Scholar 

  36. K.D. McCloskey, Characterization of outward currents in interstitial cells from the guinea pig bladder. J. Urol. 173, 296–301 (2005)

    Article  CAS  PubMed  Google Scholar 

  37. K.D. McCloskey, Calcium currents in interstitial cells from the guinea-pig bladder. BJU Int. 97, 1338–1343 (2006)

    Article  CAS  PubMed  Google Scholar 

  38. O.J. Wiseman, C.J. Fowler, D.N. Landon, The role of the human bladder lamina propria myofibroblast. BJU Int. 91, 89–93 (2003)

    Article  CAS  PubMed  Google Scholar 

  39. J.I. Gillespie, I.M. Markerink-van, J. de Vente, cGMP-generating cells in the bladder wall: identification of distinct networks of interstitial cells. BJU Int. 94, 1114–1124 (2004)

    Article  PubMed  Google Scholar 

  40. J.I. Gillespie, Endogenous nitric oxide/cGMP signalling in the guinea pig bladder: evidence for distinct populations of sub-urothelial interstitial cells. Cell Tissue Res. 325, 325 (2006)

    Article  CAS  PubMed  Google Scholar 

  41. O.J. Wiseman, C.M. Brady, I.F. Hussain, P. Dasgupta, H. Watt, C.J. Fowler, D.N. Landon, The ultrastructure of bladder lamina propria nerves in healthy subjects and patients with detrusor hyperreflexia. J. Urol. 168, 2040–2045 (2002)

    Article  PubMed  Google Scholar 

  42. G.P. Sui, C. Wu, C.H. Fry, Characterization of the purinergic receptor subtype on guinea-pig suburothelial myofibroblasts. BJU Int. 97, 1327–1331 (2006)

    Article  CAS  PubMed  Google Scholar 

  43. D. Ost, T. Roskams, A.F. Van Der, D. De Ridder, Topography of the vanilloid receptor in the human bladder: more than just the nerve fibers. J. Urol. 168, 293–297 (2002)

    Article  PubMed  Google Scholar 

  44. G.P. Sui, C. Wu, A. Roosen, Y. Ikeda, A.J. Kanai, C.H. Fry, Modulation of bladder myofibroblast activity: implications for bladder function. Am. J. Physiol. Renal Physiol. 295, F688–F697 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. C. Wu, G.P. Gui, C.H. Fry, Intracellular Ca(2+) regulation and electrophysiolgical properties of bladder urothelium subjected to stretch and exogenous agonists. Cell Calcium 49, 395–399 (2011)

    Article  CAS  PubMed  Google Scholar 

  46. L.A. Birder, H.Z. Ruan, B. Chopra, Z. Xiang, S. Barrick, C.A. Buffington, J.R. Roppolo, A.P. Ford, W.C. de Groat, G. Burnstock, Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis. Am. J. Physiol. Renal Physiol. 287, F1084–F1091 (2004)

    Article  CAS  PubMed  Google Scholar 

  47. E.C. Wang, J.M. Lee, W.G. Ruiz, E.M. Balestreire, M. von Bodungen, S. Barrick, D.A. Cockayne, L.A. Birder, G. Apodaca, ATP and purinergic receptor-dependent membrane traffic in bladder umbrella cells. J. Clin. Invest. 115, 2412–2422 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. E.L. Andrade, J. Ferreira, E. Andre, J.B. Calixto, Contractile mechanisms coupled to TRPA1 receptor activation in rat urinary bladder. Biochem. Pharmacol. 72, 104–114 (2006)

    Article  CAS  PubMed  Google Scholar 

  49. R.J. Stein, S. Santos, J. Nagatomi, Y. Hayashi, B.S. Minnery, M. Xavier, A.S. Patel, J.B. Nelson, W.J. Futrell, N. Yoshimura, M.B. Chancellor, F. De Miguel, Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J. Urol. 172, 1175–1178 (2004)

    Article  CAS  PubMed  Google Scholar 

  50. L.A. Birder, M.L. Nealen, S. Kiss, W.C. de Groat, M.J. Caterina, E. Wang, G. Apodaca, A.J. Kanai, Beta-adrenoceptor agonists stimulate endothelial nitric oxide synthase in rat urinary bladder urothelial cells. J. Neurosci. 22, 8063–8070 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. B. Chopra, S.R. Barrick, S. Meyers, J.M. Beckel, M.L. Zeidel, A.P. Ford, W.C. de Groat, L.A. Birder, Expression and function of bradykinin B1 and B2 receptors in normal and inflamed rat urinary bladder urothelium. J. Physiol. 562, 859–871 (2005)

    Article  CAS  PubMed  Google Scholar 

  52. X. Wang, Y. Momota, H. Yanase, S. Narumiya, T. Maruyama, M. Kawatani, Urothelium EP1 receptor facilitates the micturition reflex in mice. Biomed. Res. 29, 105–111 (2008)

    Article  PubMed  Google Scholar 

  53. W. Yu, L.C. Zacharia, E.K. Jackson, G. Apodaca, Adenosine receptor expression and function in bladder uroepithelium. Am. J. Physiol. Cell Physiol. 291, C254–C265 (2006)

    Article  CAS  PubMed  Google Scholar 

  54. S. Makela, L. Strauss, G. Kuiper, E. Valve, S. Salmi, R. Santti, J.A. Gustafsson, Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract. Mol. Cell. Endocrinol. 170, 219–229 (2000)

    Article  CAS  PubMed  Google Scholar 

  55. S. Du, I. Araki, Y. Mikami, H. Zakoji, M. Beppu, M. Yoshiyama, M. Takeda, Amiloride-sensitive ion channels in urinary bladder epithelium involved in mechanosensory transduction by modulating stretch-evoked adenosine triphosphate release. Urology 69, 590–595 (2007)

    Article  PubMed  Google Scholar 

  56. M.G. Dalghi, W.G. Ruiz, D.R. Clayton, N. Montalbetti, S.L. Daugherty, J.M. Beckel, M.D. Carattino, G. Apodaca, Functional roles for PIEZO1 and PIEZO2 in urothelial mechanotransduction and lower urinary tract interoception. JCI Insight 6 (2021)

    Google Scholar 

  57. M. Michishita, K. Yano, K.I. Tomita, O. Matsuzaki, K.I. Kasahara, Piezo1 expression increases in rat bladder after partial bladder outlet obstruction. Life Sci. 166, 1–7 (2016)

    Article  CAS  PubMed  Google Scholar 

  58. L.A. Birder, A. Wolf-Johnston, D. Griffiths, N.M. Resnick, Role of urothelial nerve growth factor in human bladder function. Neurourol. Urodyn. 26, 405–409 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. C. Wasen, M. Ekstrand, M. Levin, D. Giglio, Epidermal growth factor receptor function in the human urothelium. Int. Urol. Nephrol. 50, 647–656 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. M.W.G. Roberts, G. Sui, R. Wu, W. Rong, S. Wildman, B. Montgomery, A. Ali, S. Langley, M.R. Ruggieri Sr., C. Wu, TRPV4 receptor as a functional sensory molecule in bladder urothelium: Stretch-independent, tissue-specific actions and pathological implications. FASEB J. 34, 263–286 (2020)

    Article  CAS  PubMed  Google Scholar 

  61. L.A. Birder, G. Apodaca, W.C. de Groat, A.J. Kanai, Adrenergic- and capsaicin-evoked nitric oxide release from urothelium and afferent nerves in urinary bladder. Am. J. Phys. 275, F226–F229 (1998)

    CAS  Google Scholar 

  62. L.A. Birder, More than just a barrier: Urothelium as a drug target for urinary bladder pain. Am. J. Physiol. Renal Physiol. 289, F489–F495 (2005)

    Article  CAS  PubMed  Google Scholar 

  63. M. Yoshida, A. Inadome, Y. Maeda, Y. Satoji, K. Masunaga, Y. Sugiyama, S. Murakami, Non-neuronal cholinergic system in human bladder urothelium. Urology 67, 425–430 (2006)

    Article  PubMed  Google Scholar 

  64. M.L. Lacerda, M.A. Ingersoll, The immune response to infection in the bladder. Nat. Rev. Urol. 17, 439–458 (2020)

    Article  Google Scholar 

  65. L.A. Birder, Y. Nakamura, S. Kiss, M.L. Nealen, S. Barrick, A.J. Kanai, E. Wang, G. Ruiz, W.C. de Groat, G. Apodaca, S. Watkins, M.J. Caterina, Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat. Neurosci. 5, 856–860 (2002)

    Article  CAS  PubMed  Google Scholar 

  66. G. Sui, C.H. Fry, B. Montgomery, M. Roberts, R. Wu, C. Wu, Purinergic and muscarinic modulation of ATP release from the urothelium and its paracrine actions. Am. J. Physiol. Renal Physiol. 306, F286–F298 (2014)

    Article  CAS  PubMed  Google Scholar 

  67. H. Sana-Ur-Rehman, I. Markus, K.H. Moore, K.J. Mansfield, L. Liu, Expression and localization of pannexin-1 and CALHM1 in porcine bladder and their involvement in modulating ATP release. Am. J. Physiol. Regul. Integr. Comp. Physiol. 312, R763–R772 (2017)

    Article  PubMed  Google Scholar 

  68. A. Silberfeld, B. Chavez, C. Obidike, S. Daugherty, W.C. de Groat, J.M. Beckel, LPS-mediated release of ATP from urothelial cells occurs by lysosomal exocytosis. Neurourol. Urodyn. 39, 1321–1329 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Y.H. Lin, B.J. Chiang, C.H. Liao, Mechanism of action of botulinum toxin A in treatment of functional urological disorders. Toxins (Basel) 12 (2020)

    Google Scholar 

  70. B. Abbasian, A. Shair, D.B. O'Gorman, A.M. Pena-Diaz, L. Brennan, K. Engelbrecht, D.W. Koenig, G. Reid, J.P. Burton, Potential role of extracellular ATP released by bacteria in bladder infection and contractility. mSphere 4 (2019)

    Google Scholar 

  71. S.M. Brierley, K.G.K. Goh, M.J. Sullivan, K.H. Moore, G.C. Ulett, L. Grundy, Innate immune response to bacterial urinary tract infection sensitises high-threshold bladder afferents and recruits silent nociceptors. Pain 161, 202–210 (2020)

    Article  CAS  PubMed  Google Scholar 

  72. E. Okuyama, M. Kawatani, J. Hashimoto, K. Tanimoto, M. Hashimoto, K. Matsumoto-Miyai, The nitric oxide-cyclic guanosine monophosphate pathway inhibits the bladder ATP release in response to a physiological or pathological stimulus. Physiol. Rep. 9, e14938 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. N. Ueda, M. Kondo, K. Takezawa, H. Kiuchi, Y. Sekii, Y. Inagaki, T. Soda, S. Fukuhara, K. Fujita, M. Uemura, R. Imamura, Y. Miyagawa, N. Nonomura, S. Shimada, Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense. Sci. Rep. 10, 21167 (2020)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. C. Wu, G. Sui, S.N. Archer, P. Sassone-Corsi, K. Aitken, D. Bagli, Y. Chen, Local receptors as novel regulators for peripheral clock expression. FASEB J. 28, 4610–4616 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. T. Ihara, T. Mitsui, Y. Nakamura, M. Kanda, S. Tsuchiya, S. Kira, H. Nakagomi, N. Sawada, M. Kamiyama, Y. Hirayama, E. Shigetomi, Y. Shinozaki, M. Yoshiyama, A. Nakao, M. Takeda, S. Koizumi, The oscillation of intracellular Ca(2+) influx associated with the circadian expression of Piezo1 and TRPV4 in the bladder urothelium. Sci. Rep. 8, 5699 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  76. A. Sengiku, M. Ueda, J. Kono, T. Sano, N. Nishikawa, S. Kunisue, K. Tsujihana, L.S. Liou, A. Kanematsu, S. Shimba, M. Doi, H. Okamura, O. Ogawa, H. Negoro, Circadian coordination of ATP release in the urothelium via connexin43 hemichannels. Sci. Rep. 8, 1996 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  77. F. Ma, D.E. Kouzoukas, K.L. Meyer-Siegler, K.N. Westlund, D.E. Hunt, P.L. Vera, Disulfide high mobility group box-1 causes bladder pain through bladder toll-like receptor 4. BMC Physiol. 17, 6 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  78. A.L. Warburton, R.M. Santer, Sympathetic and sensory innervation of the urinary tract in young adult and aged rats: a semi-quantitative histochemical and immunohistochemical study. Histochem. J. 26, 127–133 (1994)

    Article  CAS  PubMed  Google Scholar 

  79. J. Jacob, C.M. Ludgate, J. Forde, W.S. Tulloch, Recent observations on the ultrastructure of human urothelium. 1. Normal bladder of elderly subjects. Cell Tissue Res. 193, 543–560 (1978)

    Article  CAS  PubMed  Google Scholar 

  80. J.I. Phillips, Inflammatory plasma cell infiltration of the urinary bladder in the aging C57BL/Icrfa(t) mouse. Investig. Urol. 19, 75–78 (1981)

    CAS  Google Scholar 

  81. M. Yoshida, K. Masunaga, Y. Satoji, Y. Maeda, T. Nagata, A. Inadome, Basic and clinical aspects of non-neuronal acetylcholine: expression of non-neuronal acetylcholine in urothelium and its clinical significance. J. Pharmacol. Sci. 106, 193–198 (2008)

    Article  CAS  PubMed  Google Scholar 

  82. M. Yoshida, K. Miyamae, H. Iwashita, M. Otani, A. Inadome, Management of detrusor dysfunction in the elderly: changes in acetylcholine and adenosine triphosphate release during aging. Urology 63, 17–23 (2004)

    Article  PubMed  Google Scholar 

  83. D.M. Daly, L. Nocchi, M. Liaskos, N.G. McKay, C. Chapple, D. Grundy, Age-related changes in afferent pathways and urothelial function in the male mouse bladder. J. Physiol. 592, 537–549 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. S.T. Truschel, D.R. Clayton, J.M. Beckel, J.G. Yabes, Y. Yao, A. Wolf-Johnston, L.A. Birder, G. Apodaca, Age-related endolysosome dysfunction in the rat urothelium. PLoS One 13, e0198817 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  85. N. Montalbetti, A.C. Rued, S.N. Taiclet, L.A. Birder, F.A. Kullmann, M.D. Carattino, Urothelial tight junction barrier dysfunction sensitizes bladder afferents. eNeuro 4 (2017)

    Google Scholar 

  86. L.A. Birder, W.C. de Groat, Mechanisms of disease: involvement of the urothelium in bladder dysfunction. Nat. Clin. Pract. Urol. 4, 46–54 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. V. Kumar, C.R. Chapple, A.M. Surprenant, R. Chess-Williams, Enhanced adenosine triphosphate release from the urothelium of patients with painful bladder syndrome: a possible pathophysiological explanation. J. Urol. 178, 1533–1536 (2007)

    Article  CAS  PubMed  Google Scholar 

  88. Y. Sun, T.C. Chai, Augmented extracellular ATP signaling in bladder urothelial cells from patients with interstitial cystitis. Am. J. Physiol. Cell Physiol. 290, C27–C34 (2006)

    Article  CAS  PubMed  Google Scholar 

  89. L.A. Birder, S.R. Barrick, J.R. Roppolo, A.J. Kanai, W.C. de Groat, S. Kiss, C.A. Buffington, Feline interstitial cystitis results in mechanical hypersensitivity and altered ATP release from bladder urothelium. Am. J. Physiol. Renal Physiol. 285, F423–F429 (2003)

    Article  CAS  PubMed  Google Scholar 

  90. K.J. Mansfield, L. Liu, K.H. Moore, K.J. Vaux, R.J. Millard, E. Burcher, Molecular characterization of M2 and M3 muscarinic receptor expression in bladder from women with refractory idiopathic detrusor overactivity. BJU Int. 99, 1433–1438 (2007)

    Article  CAS  PubMed  Google Scholar 

  91. V. Kumar, C.R. Chapple, D. Rosario, P.R. Tophill, R. Chess-Williams, In vitro release of adenosine triphosphate from the urothelium of human bladders with detrusor overactivity, both neurogenic and idiopathic. Eur. Urol. 57, 1087–1092 (2010)

    Article  CAS  PubMed  Google Scholar 

  92. S.N. Datta, A. Roosen, A. Pullen, R. Popat, T.P. Rosenbaum, S. Elneil, P. Dasgupta, C.J. Fowler, A. Apostolidis, Immunohistochemical expression of muscarinic receptors in the urothelium and suburothelium of neurogenic and idiopathic overactive human bladders, and changes with botulinum neurotoxin administration. J. Urol. 184, 2578–2585 (2010)

    Article  CAS  PubMed  Google Scholar 

  93. C.M. Brady, A. Apostolidis, Y. Yiangou, P.A. Baecker, A.P. Ford, A. Freeman, T.S. Jacques, C.J. Fowler, P. Anand, P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin. Eur. Urol. 46, 247–253 (2004)

    Article  CAS  PubMed  Google Scholar 

  94. C.M. Brady, A.N. Apostolidis, M. Harper, Y. Yiangou, A. Beckett, T.S. Jacques, A. Freeman, F. Scaravilli, C.J. Fowler, P. Anand, 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 (2004)

    Article  CAS  PubMed  Google Scholar 

  95. A. Roosen, S.N. Datta, R.A. Chowdhury, P.M. Patel, V. Kalsi, S. Elneil, P. Dasgupta, T.M. Kessler, S. Khan, J. Panicker, C.H. Fry, S. Brandner, C.J. Fowler, A. Apostolidis, Suburothelial myofibroblasts in the human overactive bladder and the effect of botulinum neurotoxin type A treatment. Eur. Urol. 55, 1440–1448 (2009)

    Article  CAS  PubMed  Google Scholar 

  96. Y. Wu, J. Qi, C. Wu, W. Rong, Emerging roles of the TRPV4 channel in bladder physiology and dysfunction. J. Physiol. 599, 39–47 (2021)

    Article  CAS  PubMed  Google Scholar 

  97. J.C. Kim, J.S. Yoo, E.Y. Park, S.H. Hong, S.I. Seo, T.K. Hwang, Muscarinic and purinergic receptor expression in the urothelium of rats with detrusor overactivity induced by bladder outlet obstruction. BJU Int. 101, 371–375 (2008)

    Article  CAS  PubMed  Google Scholar 

  98. Y. Ikeda, A. Kanai, Urotheliogenic modulation of intrinsic activity in spinal cord-transected rat bladders: role of mucosal muscarinic receptors. Am. J. Physiol. Renal Physiol. 295, F454–F461 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. A. Contreras-Sanz, L. Krska, A.A. Balachandran, N.L. Curtiss, R. Khasriya, S. Kelley, M. Strutt, H.S. Gill, K.M. Taylor, K.J. Mansfield, C. Wu, C.M. Peppiatt-Wildman, J. Malone-Lee, J. Duckett, S.S. Wildman, Altered urothelial ATP signaling in a major subset of human overactive bladder patients with pyuria. Am. J. Physiol. Renal Physiol. 311, F805–F816 (2016)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The author acknowledges the support from Biotechnology and Biological Sciences Research Council (BBSRC) (BB/P004695/1) and National Institute of Aging (NIA, 1R01AG049321-01A1).

Author information

Authors and Affiliations

  1. Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, UK

    Changhao Wu

Authors
  1. Changhao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Changhao Wu .

Editor information

Editors and Affiliations

  1. Department of Urology Department of Neurourology, China Rehabiliation Research Center China Rehabilitation Science InstituteCapital Medical University, Beijing, China

    Limin Liao

  2. Department of Urology, Medical University Innsbruck, University Hospital, Innsbruck, Austria

    Helmut Madersbacher

Rights and permissions

Reprints and permissions

Copyright information

© 2023 Springer Nature Singapore Pte Ltd.

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Wu, C. (2023). Sensor and Transducer Function of the Urothelium: Pathological Implications. In: Liao, L., Madersbacher, H. (eds) Handbook of Neurourology. Springer, Singapore. https://doi.org/10.1007/978-981-99-1659-7_2

Download citation

  • DOI: https://doi.org/10.1007/978-981-99-1659-7_2

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-99-1658-0

  • Online ISBN: 978-981-99-1659-7

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation