Skip to main content
SpringerLink
Log in

Urothelial Signaling

  • Chapter
  • First Online:
Urinary Tract

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 2011))

Abstract

The urinary bladder “mucosa” or innermost portion of the bladder is composed of transitional epithelium, basement membrane, and the lamina propria. This chapter reviews the specialized anatomy of the bladder epithelium (urothelium) and speculates on possible communication mechanisms from urothelial cells to various cell types within the bladder wall. For example, beyond serving as a simple barrier, there is growing evidence that the urinary bladder urothelium exhibits specialized sensory properties and plays a key role in the detection and transmission of both physiological and nociceptive stimuli. Findings from a number of studies suggest that the urothelium exhibits both “sensor” (expressing receptors/ion channels capable of responding to thermal, mechanical, and chemical stimuli) and “transducer” (ability to release chemicals) properties. Thus, urothelial cells exhibit the ability to sense changes in their extracellular environment including the ability to respond to chemical, mechanical, and thermal stimuli that may communicate the state of the urothelial environment to the underlying nervous and muscular systems.

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 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
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

Similar content being viewed by others

References

  • Abraham P, Rabi S, Selvakumar D (2009) Protective effect of aminoguanidine against oxidative stress and bladder injury in cyclophosphamide-induced hemorrhagic cystitis in rat. Cell Biochem Funct 27:56–62

    CAS  PubMed  Google Scholar 

  • Acharya P, Beckel JM, Ruiz WG, Wang E, Rojas R, Birder LA, Apodaca G (2004) Distribution of the tight junction proteins Z0-1, occludin, and claudin-4, -8, and -12 in bladder epithelium. Am J Physiol Renal Physiol 287:F305–F318

    CAS  PubMed  Google Scholar 

  • Anderson G, Palermo J, Schilling J, Roth R, Heuser J, Hultgren S (2003) Intracellular bacterial biofilm-like pods in urinary tract infections. Science 301:105–107

    CAS  PubMed  Google Scholar 

  • Andersson KE, Persson K (1995) Nitric oxide synthase and the lower urinary tract: possible implications for physiology and pathophysiology. Scand J Urol Nephrol 175:43–53

    CAS  Google Scholar 

  • Andersson KE, Fulhase C, Soler R (2008) Urothelial effects of oral agents for overactive bladder. Curr Urol Rep 9:459–464

    PubMed  Google Scholar 

  • Apodaca G (2004) The uroepithelium: not just a passive barrier. Traffic 5:117–128

    CAS  PubMed  Google Scholar 

  • Apodaca G, Kiss S, Ruiz WG, Meyers S, Zeidel M, Birder LA (2003) Disruption of bladder epithelium barrier function after spinal cord injury. Am J Physiol 284:F966–F976

    CAS  Google Scholar 

  • Apodaca G, Balestreire E, Birder LA (2007) The uroepithelial-associated sensory web. Kidney Int 72:1057–1064

    CAS  PubMed  Google Scholar 

  • Apostolidis A, Brady CM, Yiangou Y, Davis J, Fowler CJ, Anand P (2005) Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin. Urology 65:400–405

    PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Araki I, Du S, Kobayashi H, Sawada N, Mochizuki T, Zakoji H, Takeda M (2008) Roles of mechanosensitive ion channels in bladder sensory transduction and overactive bladder. Int J Urol 15:681–687

    PubMed  Google Scholar 

  • Balestreire EM, Apodaca G (2007) Apical EGF receptor signaling: regulation of stretch-dependent exocytosis in bladder umbrella cells. Mol Biol Cell 18:1312–1323

    CAS  PubMed  Google Scholar 

  • Bassuk JA, Cochrane K, Mitchell ME (2003) Induction of urothelial cell proliferation by fibroblast growth factor-7 in RAG1-deficient mice. Adv Exp Med Biol 539:623–633

    PubMed  Google Scholar 

  • Beckel JM, Kanai AJ, Lee SJ, DeGroat WC, Birder LA (2006) Expression of functional nicotinic acetylcholine receptors in rat urinary bladder epithelial cells. Am J Physiol 290:F103–F110

    CAS  Google Scholar 

  • Bidaux G, Roudbaraki M, Merle C, Crepin A, Delcourt P, Slomianny C, Thebault S, Bonnal JL, Benahmed M, Cabon F, Mauroy B, Prevarskaya N (2005) Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement. Endocr Relat Cancer 12:367–382

    CAS  PubMed  Google Scholar 

  • Billips BK, Schaeffer AJ, Klumpp DJ (2008) Molecular basis of uropathogenic Escherichia coli evasion of the innate immune response in the bladder. Infect Immun 76:3891–3900

    CAS  PubMed  Google Scholar 

  • Birder LA, de Groat WC (2007) Mechanisms of disease: involvement of the urothelium in bladder dysfunction. Nat Clin Pract 4:46–54

    CAS  Google Scholar 

  • Birder LA, Apodaca G, de Groat WC, Kanai AJ (1998) Adrenergic and capsaicin-evoked nitric oxide release from urothelium and afferent nerves in urinary bladder. Am J Physiol 275:F226–F229

    CAS  PubMed  Google Scholar 

  • Birder LA, Kanai AJ, de Groat WC, Kiss S, Nealen ML, Burke NE, Dineley KE, Watkins S, Reynolds IJ, Caterina MJ (2001) Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci 98:13396–13401

    CAS  PubMed  Google Scholar 

  • Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick SR, Kanai AJ, Wang E, Ruiz WG, de Groat WC, Apodaca G, Watkins S, Caterina MJ (2002a) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5:856–860

    CAS  PubMed  Google Scholar 

  • Birder LA, Nealen ML, Kiss S, de Groat WC, Caterina MJ, Wang E, Apodaca G, Kanai AJ (2002b) Beta-adrenoceptor agonists stimulate endothelial nitric oxide synthase in rat urinary bladder urothelial cells. J Neurosci 22:8063–8070

    CAS  PubMed  Google Scholar 

  • Birder LA, Barrick SR, Roppolo JR, Kanai AJ, de Groat WC, Kiss S, Buffington CAT (2003) Feline interstitial cystitis results in mechanical hypersensitivity and altered ATP release from bladder urothelium. Am J Physiol 285:F423–F429

    CAS  Google Scholar 

  • Birder LA, Wolf-Johnton A, Buffington CAT, Roppolo JR, de Groat WC, Kanai AJ (2005) Altered inducible nitric oxide synthase expression and nitric oxide production in the bladder of cats with feline interstitial cystitis. J Urol 173:625–629

    CAS  PubMed  Google Scholar 

  • Birder L, Kullmann FA, Lee H, Barrick S, de Groat W, Kanai A, Caterina M (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

    CAS  PubMed  Google Scholar 

  • Birder LA, Wolf-Johnston AS, Chib MK, Buffington CA, Roppolo JR, Hanna-Mitchell AT (2009) Beyond neurons: involvement of urothelial and glial cells in bladder function. Neurourol Urodyn 29:88–96

    Google Scholar 

  • Bosse Y, Pare PD, Seow CY (2008) Airway wall remodeling in asthma: from the epithelial layer to the adventitia. Curr Allergy Asthma Rep 8:357–366

    CAS  PubMed  Google Scholar 

  • Botchkarev VA, Metz M, Botchkareva NV, Welker P, Lommatzsch M, Renz H (1999) Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 act as “epitheliotrophins” in murine skin. Lab Invest 79:557–572

    CAS  PubMed  Google Scholar 

  • Brading AF, McCloskey DD (2005) Mechanisms of disease: specialized interstitial cells of the urothelium – an assessment of current knowledge. Nat Clin Pract Urol 2:546–554

    PubMed  Google Scholar 

  • Brady CM, Apostolidis AN, Harper M, Yiangou Y, Beckett A, Jacques TS, Freeman A, Scaravilli F, Fowler CJ, Anand P (2004) Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment. BJU Int 93:770–776

    CAS  PubMed  Google Scholar 

  • Buffington CA, Teng B, Somogyi GT (2002) Norepinephrine content and adrenoceptor function in the bladder of cats with feline interstitial cystitis. J Urol 167:1876–1880

    CAS  PubMed  Google Scholar 

  • Burnstock G (2001) Purine-mediated signalling in pain and visceral perception. Trends Pharmacol Sci 22:182–188

    CAS  PubMed  Google Scholar 

  • Carattino MD, Passero CJ, Steren CA, Maarouf AB, Pilewski JM, Myerburg MM, Hughey RP, Kleyman TR (2008) Defining an inhibitory domain in the alpha-subunit of the epithelial sodium channel. Am J Physiol 294:F47–F52

    CAS  Google Scholar 

  • Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824

    CAS  PubMed  Google Scholar 

  • Chai TC, Gray J, 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

    CAS  PubMed  Google Scholar 

  • Chaiyaprasithi B, Mang CF, Kilbinger H, Hohenfellner M (2003) Inhibition of human detrusor contraction by a urothelium derived factor. J Urol 170:1897–1900

    CAS  PubMed  Google Scholar 

  • Chancellor MB (2005) Urgency, botulinum toxin and how botulinum toxin can help urgency. J Urol 174:818

    PubMed  Google Scholar 

  • Chancellor MB, de Groat WC (1999) Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder. J Urol 162:3–11

    CAS  PubMed  Google Scholar 

  • Chancellor MB, Fowler CJ, Apostolidis A, de Groat WC, Smith CP, Somogyi GT, Aoki KR (2007) Drug insight: biological effects of botulinum toxin A in the lower urinary tract. Nat Clin Pract Urol 5:319–328

    Google Scholar 

  • Chang L, Karin M (2001) Mammalian MAP kinase signalling cascades. Nature 410:37–40

    CAS  PubMed  Google Scholar 

  • Chang A, Butler S, Sliwoski J, Vanentino RJ, Canning DA, Zderic SA (2009) Social stress in mice induces voiding dysfunction and bladder wall remodeling. Am J Physiol 297:F1101–F1108

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Chen Q, Takahashi S, Zhong S, Hosoda C, Zheng HY, Ogushi T, Fujimura T, Ohta N, Tanoue A, Tsujimoto G, Kitamura T (2005) Function of the lower urinary tract in mice lacking alpha1d-adrenoceptor. J Urol 174:370–374

    CAS  PubMed  Google Scholar 

  • Cheng JH, Zhang ZT (2002) Overexpression of epidermal growth factor receptor in urothelium elicits urothelial hyperplasia and promotes bladder tumor growth. Cancer Res 62:4157–4163

    CAS  PubMed  Google Scholar 

  • Cheng CL, Chai CY, de Groat WC (1997) Detrusor-sphincter dyssynergia induced by cold stimulation of the urinary bladder of rats. Am J Physiol 41:R1271–R1282

    Google Scholar 

  • Cheng JT, Yu BC, Tong YC (2007) Changes of M3-muscarinic receptor protein and mRNA expressions in the bladder urothelium and muscle layer of streptozotocin-induced diabetic rats. Neurosci Lett 423:1

    CAS  PubMed  Google Scholar 

  • Chess-Williams R (2002) Muscarinic receptors of the urinary bladder: detrusor, urothelial and prejunctional. Auton Autacoid Pharmacol 22:133–145

    CAS  PubMed  Google Scholar 

  • Chopra B, Barrick SR, Meyers S, Beckel JM, Zeidel ML, Ford AP, de Groat WC, Birder LA (2005) Expression and function of bradykinin B1 and B2 receptors in normal and inflamed rat urinary bladder urothelium. J Physiol 562:859–871

    CAS  PubMed  Google Scholar 

  • Chopra B, Gever J, Barrick SR, Hanna-Mitchell AT, Beckel JM, Ford AP, Birder LA (2008) Expression and function of rat urothelial P2Y receptors. Am J Physiol 294:F821–F829

    CAS  Google Scholar 

  • Chuang YC, Fraser MO, Yu Y, Chancellor MB, de Groat WC, Yoshimura N (2001) The role of bladder afferent pathways in bladder hyperactivity induced by the intravesical administration of nerve growth factor. J Urol 165:975–979

    CAS  PubMed  Google Scholar 

  • Combrisson H, Allix S, Robain G (2007) Influence of temperature on urethra to bladder micturition reflex in the awake ewe. Neurourol Urodyn 26:290–295

    PubMed  Google Scholar 

  • Daly D, Rong W, Chess-Williams R, Chapple C, Grundy D (2007) Bladder afferent sensitivity in wild-type and TRPV1 knockout mice. J Physiol 583:663–674

    CAS  PubMed  Google Scholar 

  • de Boer WI, Vermeij M, Diez de Medina SG, Bindels E, Radvanyi F, van der Kwast T, Chopin D (1996) Functions of fibroblast and transforming growth factors in primary organoid-like cultures of normal human urothelium. Lab Invest 75:147–156

    PubMed  Google Scholar 

  • de Groat WC, Kruse MN, Vizzard MA, Cheng CL, Araki I, Yoshimura N (1997) Modification of urinary bladder function after spinal cord injury. Adv Neurol 72:347–364

    PubMed  Google Scholar 

  • Du S, Araki I, Yoshiyama M, Nomura T, Takeda M (2007) Transient receptor potential channel A1 involved in sensory transduction of rat urinary bladder through C-fiber pathway. Urology 70:826–831

    PubMed  Google Scholar 

  • Fanti JA (1994) The lower urinary tract in women-effect of aging and menopause on continence. Exp Gerontol 29:417–422

    Google Scholar 

  • Ferguson DR, Kennedy I, Burton TJ (1997) ATP is released from rat urinary bladder epithelial cells by hydrostatic pressure changes-a possible sensory mechanism? J Physiol 505:503–511

    CAS  PubMed  Google Scholar 

  • Fovaeus M, Fujiwara M, Hogestatt ED, Persson K, Andersson KE (1999) A non-nitreregic smooth muscle relaxant factor released from rat urinary bladder by muscarinic receptor stimulation. J Urol 161:649–653

    CAS  PubMed  Google Scholar 

  • Fowler CJ, Jewkes D, McDonald WI, Lynn B, de Groat WC (1992) Intravesical capsaicin for neurogenic bladder dysfunction. Lancet 339:1239

    CAS  PubMed  Google Scholar 

  • Fowler CJ, Griffiths D, de Groat WC (2008) The neural control of micturition. Nat Rev Neurosci 9:453–466

    CAS  PubMed  Google Scholar 

  • Fraser MO, Chuang YC, Tyagi P, Yokoyama T, Yoshimura N, Huang L, de Groat WC, Chancellor MB (2003) Intravesical liposome administration-a novel treatment for hyperactive bladder in the rat. Urology 61:656–663

    PubMed  Google Scholar 

  • Fry C, Sui GP, Kanai AJ, Wu C (2007) The function of suburothelial myfibroblasts in the bladder. Neurourol Urodyn 26:914–919

    CAS  PubMed  Google Scholar 

  • Gevaert T, Vriens J, Segal A, Everaerts W, Roskams T, Talavera K, Owsianik G, Liedtke W, Daelemans D, Dewachter I, Van Leuven F, Voets T, De Ridder D, Nilius B (2007) Deletion of the transient receptor potential cation channel TRPV4 impairs murine bladder voiding. J Clin Invest 117:3453–3462

    CAS  PubMed  Google Scholar 

  • Giannantoni A, Di Stasi SM, Chancellor MB (2006) New frontiers in intravesical therapies and drug therapy. Eur Urol 50:1183–1193

    CAS  PubMed  Google Scholar 

  • Gillenwater JY, Wein AJ (1998) Summary of the national institute of arthritis, diabetes, and kidney diseases workshop on interstitial cystitis. J Urol 140:205

    Google Scholar 

  • Gillespie JI, Markerink-van Ittersum M, de Vente J (2006) Sensory collaterals, intramural ganglia and motor nerves in the guinea-pig bladder: evidence for intramural neural circuits. Cell Tissue Res 325:33–45

    CAS  PubMed  Google Scholar 

  • Girard BM, Wolf-Johnston A, Braas KM, Birder LA, May V, Vizzard MA (2008) PACAP-mediated ATP release from rat urothelium and regulation of PACAP/VIP and receptor mRNA in micturition pathways after cyclophosphamide (CYP)-induced cystitis. J Mol Neurosci 36:310–320

    CAS  PubMed  Google Scholar 

  • Gotoh M, Yoshikawa Y, Kondo AS, Kondo A, Ono Y, Ohshima S (1999) Positive bladder cooling reflex in patients with bladder outlet obstruction due to benign prostatic hyperplasia. World J Urol 17:126–130

    CAS  PubMed  Google Scholar 

  • Grol S, van Koeveringe GA, de Vente J, van Kerrebroeck PE, Gillespie JI (2008) Regional differences in sensory innervation and suburothelial interstitial cells in the bladder neck and urethra. BJU Int 102:870–877

    PubMed  Google Scholar 

  • Gupta GN, Lu SG, Gold MS, Chai TC (2009) Bladder urothelial cells from patients with interstitial cystitis have an increased sensitivity to carbachol. Neurourol Urodyn 28:1022–1027

    CAS  PubMed  Google Scholar 

  • Hall JM, Couse JF, Korach KS (2001) The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem 276:36869–36872

    CAS  PubMed  Google Scholar 

  • Hanna-Mitchell AT, Beckel JM, Barbadora S, Kanai AJ, de Groat WC, Birder LA (2007) Non-neuronal acetylcholine and urinary bladder urothelium. Life Sci 80:2298–2302

    CAS  PubMed  Google Scholar 

  • Hass MA, Nichol P, Lee L, Levin RM (2009) Estrogen modulates permeability and prostaglandin levels in the rabbit urinary bladder. Prostaglandins Leukot Essent Fatty Acids 80:125–129

    CAS  PubMed  Google Scholar 

  • Hawthorn MH, Chapple CR, Cock M, Chess-Williams R (2000) Urothelium-derived inhibitory factor(s) influences on detrusor muscle contractility. BJU Int 129:416–419

    CAS  Google Scholar 

  • Hicks M (1975) The mammalian urinary bladder: an accommodating organ. Biol Rev 50:215–246

    CAS  PubMed  Google Scholar 

  • Holgate S (2007) Epithelium dysfunction in asthma. J Allergy Clin Immunol 120:1233–1244

    CAS  PubMed  Google Scholar 

  • Holgate ST (2008) The airway epithelium is central to the pathogenesis of asthma. Allergol Int 57:1–10

    CAS  PubMed  Google Scholar 

  • Hosseini A, Ehren I, Wiklund NP (2004) Nitric oxide as an objective marker for evaluation of treatment response in patients with classic interstitial cystitis. J Urol 172:2261–2265

    CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  • Ikeda Y, Fry C, Hayashi F, Stolz D, Griffiths D, Kanai AJ (2007) Role of gap junctions in spontaneous activity of the rat bladder. Am J Physiol 293:F1018–F1025

    CAS  Google Scholar 

  • Ikeda Y, Birder L, Buffington C, Roppolo J, Kanai A (2009) Mucosal muscarinic receptors enhance bladder activity in cats with feline interstitial cystitis. J Urol 181:1415–1422

    CAS  PubMed  Google Scholar 

  • Imamov O, Yakimchuk K, Morani A, Schwend T, Wada-Hiraike O, Razumov S, Warner M, Gustafsson JA (2007) Estrogen receptor beta-deficient female mice develop a bladder phenotype resembling human interstitial cystitis. Proc Natl Acad Sci 104:9806–9809

    CAS  PubMed  Google Scholar 

  • Inoue T, Gabella G (1991) A vascular network closely linked to the epithelium of the urinary bladder of the rat. Cell Tissue Res 263:137–143

    CAS  PubMed  Google Scholar 

  • Ishihama H, Momota Y, Yanase H, Wang X, de Groat WC, Kawatani M (2006) Activation of alpha1D adrenergic receptors in rat urothelium facilitates the micturition reflex. J Urol 175:358–364

    CAS  PubMed  Google Scholar 

  • Jen PY, Dixon JS, Gosling JA (1995) Immunohistochemical localization of neuromarkers and neuropeptides in human fetal and neonatal urinary bladder. Br J Urol 75:230–235

    CAS  PubMed  Google Scholar 

  • Jiang CH, Mazieres L, Lindstrom S (2002) Cold- and menthol-sensitive C afferents of cat urinary bladder. J Physiol 543:211–220

    CAS  PubMed  Google Scholar 

  • Kalsi V, Fowler CJ (2005) Therapy insight: bladder dysfunction associated with multiple sclerosis. Nat Clin Pract Urol 2:492–501

    PubMed  Google Scholar 

  • Keay SK, Szekely Z, Conrads TP, Veenstra TD, Barchi JJ, Zhang CO, Koch KR, Michejda CJ (2004) An antiproliferative factor from interstitial cystitis patients is a frizzled 8 protein-related sialoglycopeptide. Proc Natl Acad Sci 101:11803–11808

    CAS  PubMed  Google Scholar 

  • Khandelwal P, Abraham SN, Apodaca G (2009) Cell biology and physiology of the uroepithelium. Am J Physiol 297:F1477–F1501

    CAS  Google Scholar 

  • Khera M, Somogyi GT, Kiss S, Boone TB, Smith CP (2004) Botulinum toxin A inhibits ATP release from bladder urothelium after chronic spinal cord injury. Neurochem Int 45:987–993

    CAS  PubMed  Google Scholar 

  • Kim JH, Rivas DA, Shenot PJ, Green B, Kennelly M, Erickson JR, O’Leary M, Yoshimura N, Chancellor MB (2003) Intravesical resiniferatoxin for refractory detrusor hyperreflexia: a multicenter, blinded, randomized, placebo-controlled trial. J Spinal Cord Med 26:358–363

    PubMed  Google Scholar 

  • Kim JC, Kim DB, Seo S, Park YH, Hwang TK (2004) Nerve growth factor and vanilloid receptor expression, and detrusor instability, after relieving bladder outlet obstruction in rats. BJU Int 94:915–918

    CAS  PubMed  Google Scholar 

  • Klumpp DJ, Rycyk MT, Chen MC, Thumbikat P, Sengupta S, Schaeffer AJ (2006) Uropathogenic Escherichia coli induces extrinsic and intrinsic cascades to initiate urothelial apoptosis. Infect Immun 74:5106–5113

    CAS  PubMed  Google Scholar 

  • Kolios G, Valatas V, Ward SG (2004) Nitric oxide in inflammatory bowel disease: a universal messenger in an unsolved puzzle. Immunology 113:427–437

    CAS  PubMed  Google Scholar 

  • Korkmaz A, Oter S, Sadir S, Coskun O, Topal T, Ozler M, Bilgic H (2005) Peroxynitrite may be involved in bladder damage caused by cyclophosphamide in rats. J Urol 173:1793–1796

    CAS  PubMed  Google Scholar 

  • Korosec P, Jezernik K (2000) Early cellular and ultrastructural response of the mouse urinary bladder urothelium to ischemia. Virchows Arch 436:377–383

    CAS  PubMed  Google Scholar 

  • Kullmann FA, Artim D, Beckel J, Barrick S, de Groat WC, Birder LA (2008) Heterogeneity of muscarinic receptor-mediated calcium responses in cultured urothelial cells from rat. Am J Physiol 294:F971–F981

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Kunze A, Neuhaus J, Stolzenburg JU (2006) Quantitative immunohistochemical study of the innervation of the guinea-pig lower urinary tract. BJU Int 98:424–429

    PubMed  Google Scholar 

  • Lavelle J, Meyers S, Ruiz WG, Buffington CA, Zeidel ML, Apodaca G (2000) Urothelial pathophysiological changes in feline interstitial cystitis: a human model. Am J Physiol 278:F540–F553

    CAS  Google Scholar 

  • Lavelle J, Meyers S, Ramage R, Bastacky S, Doty D, Apodaca G, Zeidel ML (2002) Bladder permeability barrier: recovery from selective injury of surface epithelial cells. Am J Physiol 283:F242–F253

    CAS  Google Scholar 

  • LeBerge J, Malley SE, Zvarova K, Vizzard MA (2006) Expression of corticotropin-releasing factor and CRF receptors in micturition pathways after cyclophosphamide-induced cystitis. Am J Physiol 291:R692–R703

    Google Scholar 

  • Lewis SA (2000) Everything you wanted to know about the bladder epithelium but were afraid to ask. Am J Physiol 278:F867–F874

    CAS  Google Scholar 

  • Li AK, Koroly MJ, Schattenkerk ME, Malt RA, Yong M (1980) Nerve growth factor: acceleration of the rate of wound healing in mice. Proc Natl Acad Sci 77:4379–4381

    CAS  PubMed  Google Scholar 

  • Liang FX, Riedel I, Deng FM, Zhou G, Wu C, Wu WR, Kon WP, Moll R, Sun TT (2001) Organization of uroplakin subunits: transmembrane topology, pair formation and plaque composition. J Biochem 355:13–18

    CAS  Google Scholar 

  • Liang FX, Bosland MC, Huang H, Romih R, Baptiste S, Deng FM, Wu XR, Shapiro E, Sun TT (2005) Cellular basis of urothelial squamous metaplasia: roles of lineage heterogeneity and cell replacement. J Cell Biol 171:835–844

    CAS  PubMed  Google Scholar 

  • Liedtke W (2005) TRPV4 plays an evolutionary conserved role in the transduction of osmotic and mechanical stimuli in live animals. Pflugers Arch 451:176–180

    CAS  PubMed  Google Scholar 

  • Lips KS, Wunsch J, Zarghooni S, Bschleipfer T, Schukowski K, Weidner W, Wessler I, Schwantes U, Koepsell H, Kummer W (2007) Acetylcholine and molecular components of its synthesis and release machinery in the urothelium. Eur Urol 51:1042–1053

    CAS  PubMed  Google Scholar 

  • Liu HT, Kuo HC (2007) Intravesical botulinum toxin A injections plus hydrodistension can reduce nerve growth factor production and control bladder pain in interstitial cystitis. Urology 70:463–468

    PubMed  Google Scholar 

  • 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 

  • Lui G, Daneshgari F (2006) Temporal diabetes- and diuresis-induced remodeling of the urinary bladder of the rat. Am J Physiol 291:R837–R843

    Google Scholar 

  • Matsuda H, Koyama H, Sato H, Sawada J, Itakura A, Tanaka A (1998) Role of nerve growth factor in cutaneous wound healing: accelerating effects in normal and healing-impaired diabetic mice. J Exp Med 187:297–306

    CAS  PubMed  Google Scholar 

  • Mayer EA, Fanselow MS (2003) Dissecting the components of the central response to stress. Nat Neurosci 6:1011–1012

    CAS  PubMed  Google Scholar 

  • Micera A, Lambiase A, Stampachiacchiere B, Bonini S, Levi-Schaffer F (2007) Nerve growth factor and tissue repair remodeling: trkA (NGFR) and p75 (NTR), two receptors one fate. Cytokine Growth Factor Rev 18:245–256

    CAS  PubMed  Google Scholar 

  • Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC, Heuser J, Hultgren SJ (1998) Induction and evasion of host defenses by type 1-pillated uropathogenic Escherichia coli. Science 282:1494–1497

    CAS  PubMed  Google Scholar 

  • Murakami S, Chapple CR, Akino H, Seller DJ, Chess-Williams R (2007) The role of the urothelium in mediating bladder responses to isoprenaline. BJU Int 99:669–673

    CAS  PubMed  Google Scholar 

  • Murray E, Malley SE, Qiao LY, Hu VY, Vizzard MA (2004) Cyclophosphamide induced cystitis alters neurotropin and receptor tyrosine kinase expression in pelvic ganglia and bladder. J Urol 172:2434–2439

    CAS  PubMed  Google Scholar 

  • Nickel JC (2003) Interstital cystitis: an elusive clincal target? J Urol 170:816–817

    PubMed  Google Scholar 

  • Ossovskaya VS, Bunnett NW (2004) Protease-activated receptors: contribution to physiology and disease. Physiol Rev 84:579–621

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Pandita RK, Mizusawa H, Andersson KE (2000) Intravesical oxyhemoglobin initiates bladder overactivity in consious, normal rats. J Urol 164:545–550

    CAS  PubMed  Google Scholar 

  • Parsons CL (2007) The role of the urinary epithelium in the pathogenesis of interstitial cystitis/prostatitis/urethritis. Urology 69:9–16

    PubMed  Google Scholar 

  • Parsons CL, Greenspan C, Moore SW, Mulholland SG (1977) Role of surface mucin in primary antibacterial defense of bladder. Urology 9:48–52

    CAS  PubMed  Google Scholar 

  • Parsons CL, Boychuk D, Jones S, Hurst R, Callahan H (1990) Bladder surface glycosaminoglycans: an epithelial permeability barrier. J Urol 143:139–142

    CAS  PubMed  Google Scholar 

  • Parsons CL, Lilly JD, Stein P (1991) Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis). J Urol 145:732–735

    CAS  PubMed  Google Scholar 

  • Parsons CL, Greenberger M, Gabal L, Bidair M, Barme G (1998) The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis. J Urol 159:1862–1867

    CAS  PubMed  Google Scholar 

  • Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A (2002) A TRP channel that senses cold stimuli and menthol. Cell 108:705–715

    CAS  PubMed  Google Scholar 

  • Proksch E, Brandner JM, Jensen JM (2008) The skin: an indispensable barrier. Exp Dermatol 17:1063–1072

    PubMed  Google Scholar 

  • Robinson D, Cardozo LD (2002) Overactive bladder in the female patient: the role of estrogens. Curr Urol Rep 3:452–457

    PubMed  Google Scholar 

  • Robinson D, Cardozo LD (2003) The role of estrogens in female lower urinary tract dysfunction. Urology 62:45–51

    PubMed  Google Scholar 

  • Romih R, Korosec P, de Mello WJ, Jezernik K (2005) Differentiation of epithelial cells in the urinary tract. Cell Tissue Res 320:259–268

    PubMed  Google Scholar 

  • Saban MR, Backer J, Backer MV, Maier J, Fowler B, Davis CA, Simpson C, Wu XR, Birder L, Freeman MR, Soker S, Hurst RE, Saban R (2008) VEGF receptors and neuropilins are expressed in the urothelial and neuronal cells in normal mouse urinary bladder and are upregulated in inflammation. Am J Physiol 295:F60–F72

    CAS  Google Scholar 

  • Sabnis AS, Reilly CA, Veranth JM, Yost GS (2008) Increased transcription of cytokine genes in human lung epithelial cells through activation of a TRPM8 variant by cold temperatures. Am J Physiol 295:L194–L200

    CAS  Google Scholar 

  • Salas NA, Somogyi GT, Gangitano DA, Boone TB, Smith CP (2007) Receptor activated bladder and spinal ATP release in neurally intact and spinal cord injured rats. Neurochem Int 50:345–350

    CAS  PubMed  Google Scholar 

  • Seki S, Sasaki K, Fraser MO, Igawa Y, Nishizawa O, Chancellor MB, de Groat WC, Yoshimura N (2002) Immunoneutralization of nerve growth factor in lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats. J Urol 168:2269–2274

    CAS  PubMed  Google Scholar 

  • Seval Y, Cakmak H, Kayisli UA, Arici A (2006) Estrogen-mediated regulation of p38 mitogen-activated protein kinase in human endometrium. J Clin Endocrinol Metab 91:2349–2357

    CAS  PubMed  Google Scholar 

  • Shiroyanagi Y, Liu B, Cao M, Agras K, Li J, Hsieh MH, Willingham EJ, Baskin LS (2007) Urothelial sonic hedgehog signaling plays an important role in bladder smooth muscle formation. Differentiation 75:968–977

    CAS  PubMed  Google Scholar 

  • Smith CP, Vemulkonda VM, Kiss S, Boone TB, Somogyi GT (2005) Enhanced ATP release from bladder urothelium during chronic inflammation: effect of botulinum toxin A. Neurochem Int 47:291–297

    CAS  PubMed  Google Scholar 

  • Song RX, Santen RJ (2006) Membrane initiated estrogen signaling in breast cancer. Biol Reprod 75:9–16

    CAS  PubMed  Google Scholar 

  • Steers WD, Tuttle JB (2006) Mechanisms of disease: the role of nerve growth factor in the pathophysiology of bladder disorders. Nat Clin Pract Urol 3:101–110

    CAS  PubMed  Google Scholar 

  • Streng T, Axelsson HE, Hedlund P, Andersson DA, Jordt SE, Bevan S, Andersson KE, Hogestatt ED, Zygmunt PM (2008) Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol 53:391–399

    CAS  PubMed  Google Scholar 

  • Sui GP, Wu C, Fry CH (2004) Electrical characteristics of suburothelial cells isolated from the human bladder. J Urol 171:938–943

    CAS  PubMed  Google Scholar 

  • Sui GP, Wu C, Fry CH (2006) Characterization of the purinergic receptor subtype on guinea-pig suburothelial myofibroblasts. BJU Int 97:914–919

    Google Scholar 

  • Sun TT (2006) Altered phenotype of cultured urothelial and other stratified epithelial cells: implications for wound healing. Am J Physiol 291:F9–F21

    CAS  Google Scholar 

  • Sun Y, Keay S, DeDeyne P, Chai TC (2001) Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis. J Urol 166:1951–1956

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Taylor AH, Al-Azzawi F (2000) Immunolocalization of oestrogen receptor beta in human tissues. J Mol Endocrinol 24:145–155

    CAS  PubMed  Google Scholar 

  • Templeman L, Chapple CR, Chess-Williams R (2002) Urothelium derived inhibitory factor and cross-talk among receptors in the trigone of the bladder of the pig. J Urol 167:742–745

    CAS  PubMed  Google Scholar 

  • Teng J, Wang ZY, Jarrard DF, Bjorling DE (2008) Roles of estrogen receptor alpha and beta in modulating urothelial cell proliferation. Endocr Relat Cancer 15:351–364

    CAS  PubMed  Google Scholar 

  • Thomas JC, DeMarco RT, Pope JC (2005) Molecular biology of ureteral bud and trigonal development. Curr Urol Rep 6:146–151

    PubMed  Google Scholar 

  • Thumbikat P, Berry RE, Schaeffer AJ, Klumpp DJ (2009) Differentiation-induced uroplakin III expression promotes urothelial cell death in response to uropathogenic E. coli. Microbes Infect 11:57–65

    CAS  PubMed  Google Scholar 

  • Tiwari A, Naruganahalli KS (2006) Current and emerging investigational medical therapies for the treatment of overactive bladder. Expert Opin Investig Drugs 15:1017–1037

    CAS  PubMed  Google Scholar 

  • Toh KL, Ng CK (2006) Urodynamic studies in the evaluation of young men presenting with lower urinary tract symptoms. Int J Urol 13:521–523

    Google Scholar 

  • Tominaga M, Wada M, Masu M (2001) Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked hyperalgesia. Proc Natl Acad Sci 98:6951–6956

    CAS  PubMed  Google Scholar 

  • Tyagi P, Thomas CA, Yoshimura N, Chancellor MB (2009) Investigations into the presence of functional beta1, beta2 and beta3-adrenoceptors in urothelium and detrusor of human bladder. Int Braz J Urol 35:76–83

    PubMed  Google Scholar 

  • van de Merwe J (2007) Interstitial cystitis and systemic autoimmune diseases. Nat Clin Pract Urol 4:8

    Google Scholar 

  • Vastag B (2006) Monoclonals expand into neural disorders. Nat Biotechnol 24:595–596

    CAS  PubMed  Google Scholar 

  • Vizzard MA (2000) Changes in urinary bladder neurotrophic factor mRNA and NGF protein following urinary bladder dysfunction. Exp Neurol 161:273–284

    CAS  PubMed  Google Scholar 

  • Walczak JS, Price TJ, Cervero F (2009) Cannabinoid CB2 receptors are expressed in the mouse urinary bladder and their activation modulates afferent bladder activity. Neuroscience 159:1154–1163

    CAS  PubMed  Google Scholar 

  • Wang ECY, Lee JM, Johnson JP, Kleyman TR, Bridges R, Apodaca G (2003) Hydrostatic pressure-regulated ion transport in bladder uroepithelium. Am J Physiol 285:F651–F663

    CAS  Google Scholar 

  • Wang EC, Lee JM, Ruiz WG, Balestreire EM, von Bodungen M, Barrick SR, Cockayne DA, Birder LA, Apodaca G (2005) ATP and purinergic receptor-dependent membrane traffic in bladder umbrella cells. J Clin Invest 115:2412–2422

    CAS  PubMed  Google Scholar 

  • Wang ZY, Wang P, Merriam FV, Bjorling DE (2008) Lack of TRPV1 inhibits cystitis-induced increased mechanical sensitivity in mice. Pain 139:158–167

    CAS  PubMed  Google Scholar 

  • Wiseman OJ, Brady CM, Hussain IF, Dasgupta P, Watt H, Fowler CJ (2002) The ultrastructure of bladder lamina propria nerves in healthy subjects and patients with detrusor hyperreflexia. J Urol 168:2040–2045

    PubMed  Google Scholar 

  • Yamaguchi O, Chapple CR (2007) Beta3-adrenoceptors in urinary bladder. Neurourol Urodyn 26:752–756

    CAS  PubMed  Google Scholar 

  • Yassin A, Saad F, Hoesl CE, Traish AM, Hammadeh M, Shabsigh R (2006) Alpha-adrenoceptors are a common denominator in the pathophysiology of erectile function and BPH/LUTS–implications for clinical practice. Andrologia 38:1–12

    CAS  PubMed  Google Scholar 

  • Yu W, Zarharia LC, Jackson EK, Apodaca G (2006) Adenosine receptor expression and function in bladder uroepithelium. Am J Physiol 291:C254–C265

    CAS  Google Scholar 

  • Yu W, Khandelwal P, Apodaca G (2009) Distinct apical and basolateral membrane requirements for stretch-induced membrane traffic at the apical surface of bladder umbrella cells. Mol Biol Cell 20:282–295

    CAS  PubMed  Google Scholar 

  • Yuridullah R, Corrow KA, Malley SE, Vizzard MA (2006) Expression of fractalkine and fractalkine receptor in urinary bladder after cyclophosphamide (CYP)-induced cystitis. Auton Neurosci 126:380–389

    PubMed  Google Scholar 

  • Zarghooni S, Wunsch J, Bodenbenner M, Bruggmann D, Grando SA, Schwantes U, Wess J, Kummer W, Lips KS (2007) Expression of muscarinic and nicotinic acetylcholine receptors in the mouse urothelium. Life Sci 80:2308–2313

    CAS  PubMed  Google Scholar 

  • Zhu Q, Ritchie J, Marouf N, Dion SB, Resnick NM, Elbadawi A, Kuchel GA (2001) Role of ovarian hormones in the pathogenesis of impaired detrusor contractility: evidence in ovariectomized rodents. J Urol 166:1136–1141

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by NIH grants (NIDDK R37 DK54824, R01 DK57284, and P50 DK64539).

Author information

Authors and Affiliations

  1. Departments of Medicine and Pharmacology, University of Pittsburgh School of Medicine, A 1207 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA, 15261, USA

    Lori A. Birder

Authors
  1. Lori A. Birder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lori A. Birder .

Editor information

Editors and Affiliations

  1. Wake Forest University, Medical Center Blvd., Winston-Salem, 27157-1088, North Carolina, USA

    Karl-Erik Andersson

  2. Academic Medical Center, Dept. Pharmacology & Pharmacotherapy, University of Amsterdam, Meibergdreef 15, Amsterdam, 1105 AZ, Netherlands

    Martin C. Michel

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Birder, L.A. (2011). Urothelial Signaling. In: Andersson, KE., Michel, M. (eds) Urinary Tract. Handbook of Experimental Pharmacology, vol 2011. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16499-6_10

Download citation

Publish with us

Policies and ethics

Search

Navigation