Skip to main content
SpringerLink
Log in

Neuropeptides in Lower Urinary Tract Function

  • Chapter
  • First Online:
Urinary Tract

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

Abstract

Numerous neuropeptide/receptor systems including vasoactive intestinal polypeptide, pituitary adenylate cyclase-activating polypeptide, calcitonin gene-related peptide, substance P, neurokinin A, bradykinin, and endothelin-1 are expressed in the lower urinary tract (LUT) in both neural and nonneural (e.g., urothelium) components. LUT neuropeptide immunoreactivity is present in afferent and autonomic efferent neurons innervating the bladder and urethra and in the urothelium of the urinary bladder. Neuropeptides have tissue-specific distributions and functions in the LUT and exhibit neuroplastic changes in expression and function with LUT dysfunction following neural injury, inflammation, and disease. LUT dysfunction with abnormal voiding, including urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain, may reflect a change in the balance of neuropeptides in bladder reflex pathways. LUT neuropeptide/receptor systems may represent potential targets for therapeutic intervention.

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

Abbreviations

AA:

Acetic acid

ATP:

Adenosine triphosphate

BOO:

Bladder outlet obstruction

CGRP:

Calcitonin gene-related peptide

CYP:

Cyclophosphamide

DRG:

Dorsal root ganglia

DSD:

Detrusor sphincter dyssynergia

EFS:

Electric field stimulation

IC:

Interstitial cystitis

ICI:

Intercontraction interval

IL:

Interleukin

IR:

Immunoreactivity

LUT:

Lower urinary tract

NGF:

Nerve growth factor

NK:

Neurokinin

NVCs:

Nonvoiding contractions

OAB:

Overactive bladder

PACAP:

Pituitary adenylate cyclase activating polypeptide

BPS:

Bladder pain syndrome

SCI:

Spinal cord injury

SP:

Substance P

VIP:

Vasoactive intestinal polypeptide

VV:

Void volume

WT:

Wildtype

References

  • Afiatpour P, Latifpour J, Takahashi W et al (2003) Developmental changes in the functional, biochemical and molecular properties of rat bladder endothelin receptors. Naunyn Schmiedebergs Arch Pharmacol 367:462–472

    CAS  PubMed  Google Scholar 

  • Ahluwalia A, Perretti M (1999) B1 receptors as a new inflammatory target. Could this B the 1? Trends Pharmacol Sci 20:100–104

    CAS  PubMed  Google Scholar 

  • Ahluwalia A, Maggi CA, Santicioli P et al (1994) Characterization of the capsaicin-sensitive component of cyclophosphamide-induced inflammation in the rat urinary bladder. Br J Pharmacol 111:1017–1022

    CAS  PubMed  Google Scholar 

  • Ahluwalia A, Giuliani S, Scotland R et al (1998) Ovalbumin-induced neurogenic inflammation in the bladder of sensitized rats. Br J Pharmacol 124:190–196

    CAS  PubMed  Google Scholar 

  • Andersson KE (1993) Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev 45:253–308

    Google Scholar 

  • Andersson KE (1999) Advances in the pharmacological control of the bladder. Exp Physiol 84:195–213

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Andersson KE (2006) Treatment-resistant detrusor overactivity-underlying pharmacology and potential mechanisms. Int J Clin Pract 60:8–16

    Google Scholar 

  • Andersson KE, Arner A (2004) Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev 84:935–986

    CAS  PubMed  Google Scholar 

  • Andersson KE, Wein AJ (2004) Pharmacology of the lower urinary tract: basis for current and future treatments of urinary incontinence. Pharmacol Rev 56:581–631

    CAS  PubMed  Google Scholar 

  • Arimura A (1998) Perspectives on pituitary adenylate cyclase activating polypeptide (PACAP) in the neuroendocrine, endocrine, and nervous systems. Jpn J Physiol 48:301–331

    CAS  PubMed  Google Scholar 

  • Arms LA, Girard BM, Vizzard MA (2009) In: Pontari M (ed) Role of the bladder urothelium in voiding dysfunction. Curr Bladder Dysfunct Rep 4:227–233

    Google Scholar 

  • Belichard P, Luccarini JM, Defrene E et al (1999) Pharmacological and molecular evidence for kinin B-1 receptor expression in urinary bladder of cyclophosphamide-treated rats. Br J Pharmacol 128:213–219

    CAS  PubMed  Google Scholar 

  • Bhoola KD, Figueroa CD, Worthy K (1992) Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev 44:1–80

    CAS  PubMed  Google Scholar 

  • Birder LA (2006) Urinary bladder urothelium: molecular sensors of chemical/thermal/mechanical stimuli. Vascul Pharmacol 45:221–226

    CAS  PubMed  Google Scholar 

  • Birder LA (2010) Urothelial signaling. Auton Neurosci 153:33–40

    CAS  PubMed  Google Scholar 

  • Bodin P, Burnstock G (2001) Evidence that release of adenosine triphosphate from endothelial cells during increased shear stress is vesicular. J Cardiovasc Pharmacol 38:900–908

    CAS  PubMed  Google Scholar 

  • Braas KM, May V, Zvara P et al (2006) Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes. Am J Physiol Regul Integr Comp Physiol 290:R951–R962

    CAS  PubMed  Google Scholar 

  • Busacchi P, Perri T, Paradisi R et al (2004) Abnormalities of somatic peptide-containing nerves supplying the pelvic floor of women with genitourinary prolapse and stress urinary incontinence. Urology 63:591–595

    CAS  PubMed  Google Scholar 

  • Callsen-Cencic P, Mense S (1997) Expression of neuropeptides and nitric oxide synthase in neurones innervating the inflamed rat urinary bladder. J Auton Nerv Syst 65:33–44

    CAS  PubMed  Google Scholar 

  • Canda AE, Cross RL, Chapple CR (2006) Pharmacology of the lower urinary tract and management of the overactive bladder. J Turk German Gynecol Assoc 7:146–158

    Google Scholar 

  • Canda AE, Cinar MG, Turna B et al (2008) Pharmacologic targets on the female urethra. Urol Int 80:341–354

    CAS  PubMed  Google Scholar 

  • Cattaruzza F, Cottrell GS, Vaksman N et al (2009) Endothelin-converting enzyme 1 promotes re-sensitization of neurokinin 1 receptor-dependent neurogenic inflammation. Br J Pharmacol 156:730–739

    CAS  PubMed  Google Scholar 

  • Chao MV, Hempstead BL (1995) p75 and Trk: a two-receptor system. Trends Neurosci 18:321–326

    CAS  PubMed  Google Scholar 

  • Chapple CR, Milner P, Moss HE et al (1992) Loss of sensory neuropeptides in the obstructed human bladder. Br J Urol 70:373–381

    CAS  PubMed  Google Scholar 

  • Cheng CL, Ma CP, de Groat WC (1995) Effect of capsaicin on micturition and associated reflexes in chronic spinal rats. Brain Res 678:40–48

    CAS  PubMed  Google Scholar 

  • Cheppudira BP, Girard BM, Malley SE et al (2008) Upregulation of vascular endothelial growth factor isoform VEGF-164 and receptors (VEGFR-2, Npn-1, and Npn-2) in rats with cyclophosphamide-induced cystitis. Am J Physiol Renal Physiol 295:F826–F836

    CAS  PubMed  Google Scholar 

  • Chopra B, Barrick SR, Meyers S et al (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 

  • Chuang YC, Fraser MO, Yu YB et al (2001) Analysis of the afferent limb of the vesicovascular reflex using neurotoxins, resiniferatoxin and capsaicin. Am J Physiol Regul Integr Comp Physiol 281:R1302–R1310

    CAS  PubMed  Google Scholar 

  • Clemow DB, Steers WD, McCarty R et al (1998) Altered regulation of bladder nerve growth factor and neurally mediated hyperactive voiding. Am J Physiol Regul Integr Comp Physiol 44:R1279–R1286

    Google Scholar 

  • Cockayne DA, Hamilton SG, Zhu QM et al (2000) Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X(3)-deficient mice. Nature 407:1011–1015

    CAS  PubMed  Google Scholar 

  • de Groat WC (1975) Nervous control of the urinary bladder of the cat. Brain Res 87:201–211

    PubMed  Google Scholar 

  • de Groat WC (1987) Neuropeptides in pelvic afferent pathways. Experientia 43:801–813

    PubMed  Google Scholar 

  • de Groat WC, Kruse MN (1993) Central processing and morphological plasticity in lumbosacral afferent pathways from the lower urinary tract. In: Mayer EA, Raybould HE (eds) Basic and clinical aspects of chronic abdominal pain. Pain research and clinical management, vol 9. Elsevier Science, Amsterdam, pp 219–235.

    Google Scholar 

  • de Groat WC, Steers WD (1990) Autonomic regulation of the urinary bladder and sex organs. In: Loewy AD, Spyer KM (eds) Central regulation of autonomic functions. Oxford University Press, London, pp 310–333

    Google Scholar 

  • de Groat WC, Yoshimura N (2009) Afferent nerve regulation of bladder function in health and disease. In: Canning BJ, Spina D (eds) Handbook of experimental pharmacology, Sensory nerves. Springer, Berlin, pp 91–138

    Google Scholar 

  • de Groat WC, Nadelhaft I, Milne RJ et al (1981) Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine. J Auton Nerv Syst 3:135–160

    PubMed  Google Scholar 

  • de Groat WC, Kawatani M, Hisamitsu T et al (1986) Neural control of micturition: the role of neuropeptides. J Auton Nerv Syst suppl:369–387

    Google Scholar 

  • de Groat WC, Booth AM, Yoshimura N (1993) Neurophysiology of micturition and its modification in animal models of human disease. In: Maggi CA (ed) The autonomic nervous system, vol 3. Harwood Academic, London, pp 227–290

    Google Scholar 

  • de Groat WC, Vizzard MA, Araki I et al (1996) Spinal interneurons and preganglionic neurons in sacral autonomic reflex pathways. Prog Brain Res 107:97–111

    Google Scholar 

  • de Groat WC, Kruse MN, Vizzard MA et al (1997) Modification of urinary bladder function after spinal cord injury. In: Seil FJ (ed) Advances in neurology, vol 72. Raven, New York, pp 347–364

    Google Scholar 

  • Dickinson T, Mitchell R, Robberecht P et al (1999) The role of VIP/PACAP receptor subtypes in spinal somatosensory processing in rats with an experimental peripheral mononeuropathy. Neuropharmacology 38:167–180

    CAS  PubMed  Google Scholar 

  • Dmitrieva N, McMahon SB (1996) Sensitisation of visceral afferents by nerve growth factor in the adult rat. Pain 66:87–97

    CAS  PubMed  Google Scholar 

  • Donovan MK, Winternitz SR, Wyss JM (1983) An analysis of the sensory innervation of the urinary system of the rat. Brain Res Bull 11:321–324

    CAS  PubMed  Google Scholar 

  • Dray A, Perkins M (1993) Bradykinin and inflammatory pain. Trends Neurosci 16:99–104

    CAS  PubMed  Google Scholar 

  • Dupont MC, Spitsbergen JM, Kim KB et al (2001) Histological and neurotrophic changes triggered by varying models of bladder inflammation. J Urol 166:1111–1118

    CAS  PubMed  Google Scholar 

  • Ek A, Alm P, Andersson KE et al (1977) Adrenergic and cholinergic nerves of the human urethra and urinary bladder. Acta Physiol Scand 99:345–352

    CAS  PubMed  Google Scholar 

  • Erol K, Ulak G, Donmez T et al (1992) Effects of vasoactive intestinal polypeptide on isolated rat urinary bladder smooth muscle. Urol Int 49:151–153

    CAS  PubMed  Google Scholar 

  • Fabiyi AC, Brading AF (2006) The use of the isolated mouse whole bladder for investigating bladder overactivity. J Pharmacol Exp Ther 319:1386–1394

    CAS  PubMed  Google Scholar 

  • Fahrenkrug J, Hannibal J (1998) Pituitary adenylate cyclase activating polypeptide immunoreactivity in capsaicin-sensitive nerve fibres supplying the rat urinary tract. Neuroscience 83:1261–1272

    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 

  • Garcia-Pascual A, Larsson B, Andersson KE (1990) Contractile effects of endothelin-1 and localization of endothelin binding sites in rabbit lower urinary tract smooth muscle. Acta Physiol Scand 140:545–555

    CAS  PubMed  Google Scholar 

  • Girard BM, Wolf-Johnston A, Braas KM et al (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 

  • Girard BM, Galli JR, Young BA, Vizzard MA, Parsons RL (2010a) PACAP expression in explant cultured mouse major pelvic ganglia. J Mol Neurosci. doi:10.1007/s12031-010-9359-4

    Google Scholar 

  • Girard BM, Malley SE, Braas KM, May V, Vizzard MA (2010b) PACAP/VIP and receptor characterization in micturition pathways in mice with overexpression of NGF in urothelium. J Mol Neurosci. doi:10.1007/s12031-010-9384-3

    Google Scholar 

  • Giuliani S, Patacchini R, Giachetti A et al (1993a) In vivo and in vitro activity of SR 48, 968, a non-peptide tachykinin NK-2 receptor antagonist. Regul Pept 46:314–316

    CAS  PubMed  Google Scholar 

  • Giuliani S, Santicioli P, Lippe IT et al (1993b) Effect of bradykinin and tachykinin receptor antagonist on xylene-induced cystitis in rats. J Urol 150:1014–1017

    CAS  PubMed  Google Scholar 

  • Gu BJ, Ishizuka O, Igawa Y et al (2000) Role of supraspinal tachykinins for micturition in conscious rats with and without bladder outlet obstruction. Naunyn Schmied Arch Pharmacol 361:543–548

    CAS  Google Scholar 

  • Han JH, Lee MY, Myung SC (2009) The effect of endothelin-1 on the production of interleukin-6 in cultured human detrusor smooth muscle cells, and the effect of interleukin-6 on the contractile response of bladder smooth muscle strips from rats. BJU Int 104:707–712

    CAS  PubMed  Google Scholar 

  • Hernandez M, Barahona MV, Recio P et al (2006) Neuronal and smooth muscle receptors involved in the PACAP- and VIP-induced relaxations of the pig urinary bladder neck. Br J Pharmacol 149:100–109

    CAS  PubMed  Google Scholar 

  • Ho N, Koziol JA, Parsons CL (1997) Epidemiology of interstitial cystitis. In: Sant GR (ed) Interstitial cystitis. Lippincott-Raven, Philadelphia, pp 9–16

    Google Scholar 

  • Hokfelt T, Zhang X, Wiesenfeld-Hallin Z (1994) Messenger plasticity in primary sensory neurons following axotomy and its functional implications. Trends Neurosci 17:22–30

    CAS  PubMed  Google Scholar 

  • Holstege G (2005) Micturition and the soul. J Comp Neurol 493:15–20

    PubMed  Google Scholar 

  • Hutchins B, Spears R, Hinton RJ et al (2000) Calcitonin gene-related peptide and substance P immunoreactivity in rat trigeminal ganglia and brainstem following adjuvant-induced inflammation of the temporomandibular joint. Arch Oral Biol 45:335–345

    CAS  PubMed  Google Scholar 

  • Igawa Y, Persson K, Andersson KE et al (1993) Facilitatory effect of vasoactive intestinal polypeptide on spinal and peripheral micturition reflex pathways in conscious rats with and without detrusor instability. J Urol 149:884–889

    CAS  PubMed  Google Scholar 

  • Ishizuka O, Alm P, Larsson B et al (1995a) Facilitatory effect of pituitary adenylate cyclase-activating polypeptide on micturition in normal, conscious rats. Neuroscience 66:1009–1014

    CAS  PubMed  Google Scholar 

  • Ishizuka O, Mattiasson A, Andersson KE (1995b) Tachykinin effects on bladder activity in conscious normal rats. J Urol 154:257–261

    CAS  PubMed  Google Scholar 

  • Johansson SL, Fall M (1994) Pathology of interstitial cystitis. In: Hanno PM (ed) Interstitial cystitis. Proc Urol Clin N Am 21:55–62

    Google Scholar 

  • Johansson SL, Ogawa K, Fall M (1997) The pathology of interstitial cystitis. In: Sant GR (ed) Interstitial cystitis. Lippincott-Raven, Philadelphia, pp 143–152

    Google Scholar 

  • Kataeva G, Agro A (1994) Substance-P-mediated intestinal inflammation: inhibitory effects of CP 96, 345 and SMS 201–995. Neuroimmunomodulation 1:350–356

    CAS  PubMed  Google Scholar 

  • Kawatani M, Takeshige C, de Groat W (1990) Central distribution of afferent pathways from the uterus of the cat. J Comp Neurol 302:294–304

    CAS  PubMed  Google Scholar 

  • Keast JR (1991) Patterns of co-existence of peptides and differences of nerve fibre types associated with noradrenergic and non-noradrenergic (putative cholinergic) neurons in the major pelvic ganglion of the male rat. Cell Tissue Res 266:405–415

    CAS  PubMed  Google Scholar 

  • Keast JR (1992) Location and peptide content of pelvic neurons supplying the muscle and lamina propria of the rat vas deferens. J Auton Nerv Syst 40:1–12

    CAS  PubMed  Google Scholar 

  • Keast JR, de Groat WC (1992) Segmental distribution and peptide content of primary afferent neurons innervating the urogenital organs and colon of male rats. J Comp Neurol 319:615–623

    CAS  PubMed  Google Scholar 

  • Khan MA, Dashwood MR, Thompson CS et al (1999) Up-regulation of endothelin-B (ETB) receptors and ETB receptor-mediated rabbit detrusor contraction in partial bladder outlet obstruction. BJU Int 84:714–719

    CAS  PubMed  Google Scholar 

  • Kiss S, Yoshiyama M, Cao YQ et al (2001) Impaired response to chemical irritation of the urinary tract in mice with disruption of the preprotachykinin gene. Neurosci Lett 313:57–60

    CAS  PubMed  Google Scholar 

  • Klück P (1980) The autonomic innervation of the human urinary bladder neck and urethra: a histochemical study. Anat Rec 198:439–447

    PubMed  Google Scholar 

  • Kullmann FA, Artim D, Birder LA et al (2008) Activation of muscarinic receptors in rat bladder sensory pathways alters reflex bladder activity. J Neurosci 28:1977–1987

    CAS  PubMed  Google Scholar 

  • Kuru M (1965) Nervous control of micturition. Physiol Rev 45:425–494

    CAS  PubMed  Google Scholar 

  • Langenstroer P, Tang R, Divish B et al (1997) Endothelins in canine genitourinary tissues. J Urol 157:1044–1048

    CAS  PubMed  Google Scholar 

  • Lanteri-Minet M, Bon K, de Pommery J et al (1995) Cyclophosphamide cystitis as a model of visceral pain in rats: model elaboration and spinal structures involved as revealed by the expression of c-Fos and Krox-24 proteins. Exp Brain Res 105:220–232

    CAS  PubMed  Google Scholar 

  • Lapchak PA, Araujo DM, Hefti F (1992) Neurotrophins in the central nervous system. Rev Neurosci 3:1–10

    Google Scholar 

  • Latifpour J, Fukumoto Y, Weiss RM (1995) Regional differences in the density and subtype specificity of endothelin receptors in rabbit urinary tract. Naunyn Schmiedebergs Arch Pharmacol 352:459–468

    CAS  PubMed  Google Scholar 

  • Lecci A, Giuliani S, Garret C et al (1993) Evidence for a role of tachykinins as sensory transmitters in the activation of micturition reflex. Neuroscience 54:827–837

    CAS  PubMed  Google Scholar 

  • Lecci A, Giulani S, Santiciolo P et al (1994) Involvement of spinal tachykinin NK1 and NK2 receptors in detrusor hyperreflexia during chemical cystitis in anaesthetized rats. Eur J Pharmacol 259:129–135

    CAS  PubMed  Google Scholar 

  • Lecci A, Giuliani S, Meini S et al (1995) Pharmacological analysis of the local and reflex responses to bradykinin on rat urinary bladder motility in vivo. Br J Pharmacol 114:708–714

    CAS  PubMed  Google Scholar 

  • Lecci A, Meini S, Tramontana M et al (1999) Kinin B-1 receptor-mediated motor responses in normal or inflamed rat urinary bladder in vivo. Regul Pept 80:41–47

    CAS  PubMed  Google Scholar 

  • Lincoln J, Burnstock G (1993) Autonomic innervation of the urinary bladder and urethra. In: Maggi CA (ed) The autonomic nervous system, vol 3. Harwood Academic, London, pp 33–68

    Google Scholar 

  • Lindsay RM, Shooter EM, Radeke MJ et al (1990) Nerve growth factor regulates expression of the nerve growth factor gene in adult sensory neurons. Eur J Neurosci 2:389–396

    PubMed  Google Scholar 

  • Luber-Narod J, Austin-Ritchie T, Hollins C et al (1997) Role of substance P in several models of bladder inflammation. Urol Res 25:395–399

    CAS  PubMed  Google Scholar 

  • Maggi CA (1991) The role of neuropeptides in the regulation of the micturition reflex: an update. Gen Pharmacol 22:1–24

    CAS  PubMed  Google Scholar 

  • Maggi CA (1992) The dual function of capsaicin-sensitive sensory nerves in the bladder and urethra. In: Maggi CA (Ed.) The autonomic nervous system. Nervous control of the urogenital system, vol. 2. Harwood Academic, London

    Google Scholar 

  • Maggi CA (1995) Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves. Prog Neurobiol 45:1–98

    CAS  PubMed  Google Scholar 

  • Maggi CA, Santicioli P, Geppeti S et al (1988) Biochemical, anatomical and functional correlates of postnatal developments of the capsaicin-sensitive innervation of the rat urinary bladder. Dev Brain Res 43:183–190

    CAS  Google Scholar 

  • Maggi CA, Giuliani S, Patacchini R et al (1989) Potent contractile activity of endothelin on the human isolated urinary bladder. Br J Pharmacol 96:755–757

    CAS  PubMed  Google Scholar 

  • Maggi CA, Lecci A, Santiciolo P et al (1992) Cyclophosphamide cystitis in rats: involvement of capsaicin-sensitive primary afferents. J Auton Nerv Syst 38:201–208

    CAS  PubMed  Google Scholar 

  • Marceau F, Hess JF, Bachvarov DR (1998) The B1 receptors for kinins. Pharmacol Rev 50:357–386

    CAS  PubMed  Google Scholar 

  • Marchand JE, Sant GR, Kream RM (1998) Increased expression of substance P receptor-encoding mRNA in bladder biopsies from patients with interstitial cystitis. Br J Urol 81:224–228

    CAS  PubMed  Google Scholar 

  • Marson L (1997) Identification of central nervous system neurons that innervate the bladder body, bladder base, or external urethral sphincter of female rats: a transneuronal tracing study using pseudorabies virus. J Comp Neurol 389:584–602

    CAS  PubMed  Google Scholar 

  • Martinez-Garcia R, Abadias M, Arano P et al (2008) Cizolirtine citrate, an effective treatment for symptomatic patients with urinary incontinence secondary to overactive bladder: a pilot dose-finding study. Eur Urol 56:184–192

    PubMed  Google Scholar 

  • May V, Vizzard MA (2010) Urinary bladder dysfunction and altered somatic sensitivity in pituitary adenylate cyclase activating polypeptide knockout (PACAP-/-) mice. J Urol 183:772–779

    PubMed  Google Scholar 

  • Meini S, Patacchini R, Giuliani S et al (2000) Characterization of bradykinin B(2) receptor antagonists in human and rat urinary bladder. Eur J Pharmacol 388:177–182

    CAS  PubMed  Google Scholar 

  • Mersdorf A, Schmidt RA, Kaula N et al (1992) Intrathecal administration of substance P in the rat: the effect on bladder and urethral sphincteric activity. Urology 40:87–96

    CAS  PubMed  Google Scholar 

  • Middleton JW, Keast JR (2004) Artificial autonomic reflexes: using functional electrical stimulation to mimic bladder reflexes after injury or disease. Auton Neurosci 113:3–15

    PubMed  Google Scholar 

  • Mohammed H, Hannibal J, Fahrenkrug J et al (2002) Distribution and regional variation of pituitary adenylate cyclase activating polypeptide and other neuropeptides in the rat urinary bladder and ureter: effects of age. Urol Res 30:248–255

    CAS  PubMed  Google Scholar 

  • Morgan C, Nadelhaft I, de Groat WC (1981) The distribution of visceral primary afferents from the pelvic nerve within Lissauer’s tract and the spinal gray matter and its relationship to the sacral parasympathetic nucleus. J Comp Neurol 201:415–440

    CAS  PubMed  Google Scholar 

  • Morrison JFB (1987) Reflex control of the lower urinary tract. In: Torrens M, Morrison JFB (eds) The physiology of the lower urinary tract. Springer, New York

    Google Scholar 

  • Nadelhaft I, Vera PL (1995) Central nervous system neurons infected by pseudorabies virus injected into the rat urinary bladder following unilateral transection of the pelvic nerve. J Comp Neurol 359:443–456

    CAS  PubMed  Google Scholar 

  • Novak I (2003) ATP as a signaling molecule: the exocrine focus. News Physiol Sci 18:12–17

    CAS  PubMed  Google Scholar 

  • Ogawa T, Kamo I, Pflug BR et al (2004) Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats. J Urol 172:1533–1537

    CAS  PubMed  Google Scholar 

  • Ogawa T, Sasatomi K, Hiragata S et al (2008) Therapeutic effects of endothelin-A receptor antagonist on bladder overactivity in rats with chronic spinal cord injury. Urology 71:341–345

    PubMed  Google Scholar 

  • Oppenheim RW, Prevette D, Qin-Wei Y et al (1991) Control of embryonic motoneuron survival in vivo by ciliary neurotrophic factor. Science 251:1616–1618

    CAS  PubMed  Google Scholar 

  • Palea S, Corsi M, Artibani W et al (1996) Pharmacological characterization of tachykinin NK2 receptors on isolated human urinary bladder, prostatic urethra and prostate. J Pharmacol Exp Ther 277:700–705

    CAS  PubMed  Google Scholar 

  • Pang X, Marchand J, Sant GR et al (1995) Increased number of substance P positive nerve fibres in interstitial cystitis. Br J Urol 75:744–750

    CAS  PubMed  Google Scholar 

  • Parlani M, Conte B, Cirillo R et al (1996) Characterization of tachykinin NK2 receptor on dog proximal colon. Antagonism by MEN 10, 627 and SR 48, 968. Eur J Pharmacol 318:419–424

    CAS  PubMed  Google Scholar 

  • Persson K, Garcia-Pascual A, Holmquist F et al (1992) Endothelin-1-induced contractions of isolated pig detrusor and vesical arterial smooth muscle: calcium dependence and phosphoinositide hydrolysis. Gen Pharmacol 23:445–453

    CAS  PubMed  Google Scholar 

  • Ruggieri MR, Wang J, Whitmore KE (1997) Expression of bradykinin 1 receptor subtype in interstitial cystitis bladder biopsies. J Urol 157:131–136

    Google Scholar 

  • Saenz de Tejada I, Mueller JD, de Las MA et al (1992) Endothelin in the urinary bladder. I. Synthesis of endothelin-1 by epithelia, muscle and fibroblasts suggests autocrine and paracrine cellular regulation. J Urol 148:1290–1298

    CAS  PubMed  Google Scholar 

  • Schnegelsberg B, Sun TT, Cain G et al (2010) Overexpression of NGF in mouse urothelium leads neuronal hyperinnervation, pelvic sensitivity and changes in urinary bladder function. Am J Physiol Reg Integr Comp 298:R534–R547

    CAS  Google Scholar 

  • Schroder A, Tajimi M, Matsumoto H et al (2004) Protective effect of an oral endothelin converting enzyme inhibitor on rat detrusor function after outlet obstruction. J Urol 172:1171–1174

    PubMed  Google Scholar 

  • Sherwood NM, Krueckl SL, McRory JE (2000) The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon superfamily. Endocr Rev 21:619–670

    CAS  PubMed  Google Scholar 

  • Smet PJ, Moore KH, Jonavicius J (1997) Distribution and colocalization of calcitonin gene-related peptide, tachykinins, and vasoactive intestinal peptide in normal and idiopathic unstable human urinary bladder. Lab Invest 77:37–49

    CAS  PubMed  Google Scholar 

  • Steers WD, de Groat WC (1988) Effect of bladder outlet obstruction on micturition reflex pathways in the rat. J Urol 140:864–871

    CAS  PubMed  Google Scholar 

  • Steers WD, Ciambotti J, Etzel B et al (1991a) Alterations in afferent pathways from the urinary bladder of the rat in response to partial urethral obstruction. J Comp Neurol 310:1–10

    Google Scholar 

  • Steers WD, Kolbeck S, Creedon D (1991b) Nerve growth factor in the urinary bladder of the adult regulates neuronal form and function. J Clin Invest 88:1709–1715

    CAS  PubMed  Google Scholar 

  • Studeny S, Cheppudira BP, Meyers S et al (2008) Urinary bladder function and somatic sensitivity in vasoactive intestinal polypeptide (VIP)-/- mice. J Mol Neurosci 36:175–187

    CAS  PubMed  Google Scholar 

  • Su HC, Polak JM, Mulderry PK et al (1986) Calcitonin gene-related peptide immunoreactivity in afferent neurons supplying the urinary tract: combined retrograde tracing and immunohistochemistry. Neuroscience 18:727–747

    CAS  PubMed  Google Scholar 

  • Tompkins JD, Girard BM, Vizzard MA, Parsons RL (2010) VIP and PACAP effects on mouse major pelvic ganglia neurons. J Mol Neurosci. doi:10.1007/s12031-010-9367-4

    PubMed  Google Scholar 

  • Traub RJ, Hutchcroft K, Gebhart GF (1999) The peptide content of colonic afferents decreases following colonic inflammation. Peptides 20:267–273

    CAS  PubMed  Google Scholar 

  • Tuttle JB, Steers WD (1992) Nerve growth factor responsiveness of cultured pelvic ganglion neurons from the adult rat. Brain Res 588:29–40

    CAS  PubMed  Google Scholar 

  • Tuttle JB, Steers WD, Albo M (1994) Neural input regulates tissue NGF and growth of the adult rat urinary bladder. J Auton Nerv Syst 49:147–158

    CAS  PubMed  Google Scholar 

  • Uckert S, Stief CG, Lietz B et al (2002) Possible role of bioactive peptides in the regulation of human detrusor smooth muscle – functional effects in vitro and immunohistochemical presence. World J Urol 20:244–249

    PubMed  Google Scholar 

  • Ukai M, Yuyama H, Noguchi Y et al (2006) Participation of endogenous endothelin and ETA receptor in premicturition contractions in rats with bladder outlet obstruction. Naunyn Schmiedebergs Arch Pharmacol 373:197–203

    CAS  PubMed  Google Scholar 

  • Ukai M, Yuyama H, Fujimori A et al (2008) In vitro and in vivo effects of endothelin-1 and YM598, a selective endothelin ET A receptor antagonist, on the lower urinary tract. Eur J Pharmacol 580:394–400

    CAS  PubMed  Google Scholar 

  • Vantini G, Skaper SD (1992) Neurotrophic factors: from physiology to pharmacology. Pharmacol Res 26:1–15

    CAS  PubMed  Google Scholar 

  • Vizzard MA (2000a) Alterations in spinal Fos protein expression induced by bladder stimulation following cystitis. Am J Physiol Regul Integr Comp 278:R1027–R1039

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Vizzard MA (2000c) Increased expression of spinal cord Fos protein induced by bladder stimulation after spinal cord injury. Am J Physiol Regul Integr Comp 279:R295–R305

    CAS  Google Scholar 

  • Vizzard MA (2000d) Up-regulation of pituitary adenylate cyclase-activating polypeptide in urinary bladder pathways after chronic cystitis. J Comp Neurol 420:335–348

    CAS  PubMed  Google Scholar 

  • Vizzard MA (2001) Alterations in neuropeptide expression in lumbosacral bladder pathways following chronic cystitis. J Chem Neuroanat 21:125–138

    CAS  PubMed  Google Scholar 

  • Vizzard MA (2006) Neurochemical plasticity and the role of neurotrophic factors in bladder reflex pathways after spinal cord injury. Prog Brain Res 152:97–115

    CAS  PubMed  Google Scholar 

  • Vizzard MA, de Groat WC (1996) Increased expression of neuronal nitric oxide synthase (NOS) in bladder afferent pathways following chronic bladder irritation. J Comp Neurol 370:191–202

    CAS  PubMed  Google Scholar 

  • Vizzard MA, Erdman SL, de Groat WC (1993a) Localization of NADPH-diaphorase in bladder afferent and postganglionic efferent neurons of the rat. J Auton Nerv Syst 44:85–90

    CAS  PubMed  Google Scholar 

  • Vizzard MA, Erdman SL, de Groat WC (1993b) Localization of NADPH-diaphorase in pelvic afferent and efferent pathways of the rat. Neurosci Lett 152:72–76

    CAS  PubMed  Google Scholar 

  • Vizzard MA, Erdman SL, Förstermann U et al (1994) Differential distribution of nitric oxide synthase in neural pathways to the urogenital organs (urethra, penis, urinary bladder) of the rat. Brain Res 646:279–291

    CAS  PubMed  Google Scholar 

  • Vizzard MA, Erdman SL, de Groat WC (1995) Increased expression of neuronal nitric oxide synthase in dorsal root ganglion neurons after systemic capsaicin administration. Neuroscience 67:1–5

    CAS  PubMed  Google Scholar 

  • Wada Y, Latifpour J, Sanematsu H et al (2000) Age-related changes in contractile responses of rabbit lower urinary tract to endothelin. J Urol 164:806–813

    CAS  PubMed  Google Scholar 

  • Wanigasekara Y, Kepper ME, Keast JR (2003) Immunohistochemical characterisation of pelvic autonomic ganglia in male mice. Cell Tissue Res 311:175–185

    PubMed  Google Scholar 

  • Wu XR, Kong XP, Pellicer A et al (2009) Uroplakins in urothelial biology, function, and disease. Kidney Int 75:1153–1165

    CAS  PubMed  Google Scholar 

  • Yoshimura N, Bennett NE, Hayashi Y et al (2006) Bladder overactivity and hyperexcitability of bladder afferent neurons after intrathecal delivery of nerve growth factor in rats. J Neurosci 26:10847–10855

    CAS  PubMed  Google Scholar 

  • Yoshimura N, Kaiho Y, Miyazato M et al (2008) Therapeutic receptor targets for lower urinary tract dysfunction. Naunyn Schmiedebergs Arch Pharmacol 377:437–448

    CAS  PubMed  Google Scholar 

  • Yoshiyama M, de Groat WC (1997) Effects of intrathecal administration of pituitary adenylate cyclase-activating polypeptide (PACAP) on the lower urinary tract in the rat. Soc Neurosci Abstr 23:1523

    Google Scholar 

  • Yoshiyama M, de Groat WC (2008a) Effects of intrathecal administration of pituitary adenylate cyclase activating polypeptide on lower urinary tract functions in rats with intact or transected spinal cords. Exp Neurol 211:449–455

    CAS  PubMed  Google Scholar 

  • Yoshiyama M, de Groat WC (2008b) The role of vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating polypeptide in the neural pathways controlling the lower urinary tract. J Mol Neurosci 36:227–240

    CAS  PubMed  Google Scholar 

  • Zat’ura F, Vsetica J, Abadias M et al (2010) Cizolirtine citrate is safe and effective for treating urinary incontinence secondary to overactive bladder: a phase 2 proof-of-concept study. Eur Urol 57:145–152

    PubMed  Google Scholar 

  • Zvara P, Vizzard MA (2007) Exogenous overexpression of nerve growth factor in the urinary bladder produces bladder overactivity and altered micturition circuitry in the lumbosacral spinal cord. BMC Physiol 7:9

    PubMed  Google Scholar 

  • Zvara P, Braas KM, May V et al (2006) A role for pituitary adenylate cyclase activating polypeptide (PACAP) in detrusor hyperreflexia after spinal cord injury (SCI). Ann N Y Acad Sci 1070:622–628

    CAS  PubMed  Google Scholar 

  • Zvarova K, Dunleavy JD, Vizzard MA (2005) Changes in pituitary adenylate cyclase activating polypeptide expression in urinary bladder pathways after spinal cord injury. Exp Neurol 192:46–59

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors’ research described within was funded by NIH grants DK051369, DK060481, and DK065989. NIH Grant Number P20 RR16435 from the COBRE Program of the National Center also supported the project for research resources. The authors thank current and former members of the Vizzard laboratory who have contributed to the studies described within including: Beatrice Girard, Mary Beth Klinger, Susan Malley, Abbey Peterson, Kimberly Corrow, Katarina Zvarova, Peter Zvara, Li-ya Qiao, and Bopaiah P. Cheppudira. Gratitude is expressed to Emily McLaughlin for assistance with artwork production.

Author information

Authors and Affiliations

  1. Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, VT, 05405, USA

    Lauren Arms & Margaret A. Vizzard

  2. Department of Neurology, University of Vermont College of Medicine, Burlington, VT, 05405, USA

    Margaret A. Vizzard

Authors
  1. Lauren Arms
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Margaret A. Vizzard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Margaret A. Vizzard .

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

Arms, L., Vizzard, M.A. (2011). Neuropeptides in Lower Urinary Tract Function. 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_19

Download citation

Publish with us

Policies and ethics

Search

Navigation