Skip to main content
SpringerLink
Log in

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

  • Chapter
  • First Online:
Pituitary Adenylate Cyclase Activating Polypeptide — PACAP

Part of the book series: Current Topics in Neurotoxicity ((Current Topics Neurotoxicity,volume 11))

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide widely distributed throughout the body, including the gastrointestinal tract. Several effects have been described in human and animal intestines. Among others, PACAP influences secretion of intestinal glands, blood flow, and smooth muscle contraction. PACAP is a well-known cytoprotective peptide with strong anti-apoptotic, anti-inflammatory, and antioxidant effects. The present review gives an overview of the intestinal protective actions of this neuropeptide. Exogenous PACAP treatment was protective in a rat model of small bowel autotransplantation. Radioimmunoassay (RIA) analysis of the intestinal tissue showed that endogenous PACAP levels gradually decreased with longer-lasting ischemic periods, prevented by PACAP addition. PACAP counteracted deleterious effects of ischemia on oxidative stress markers and cytokines. Another series of experiments investigated the role of endogenous PACAP in intestines in PACAP knockout (KO) mice. Warm ischemia–reperfusion injury and cold preservation models showed that the lack of PACAP caused a higher vulnerability against ischemic periods. Changes were more severe in PACAP KO mice at all examined time points. This finding was supported by increased levels of oxidative stress markers and decreased expression of antioxidant molecules. PACAP was proven to be protective not only in ischemic but also in inflammatory bowel diseases. A recent study showed that PACAP treatment prolonged survival of Toxoplasma gondii infected mice suffering from acute ileitis and was able to reduce the ileal expression of proinflammatory cytokines. We completed the present review with recent clinical results obtained in patients suffering from inflammatory bowel diseases. It was found that PACAP levels were altered depending on the activity, type of the disease, and antibiotic therapy, suggesting its probable role in inflammatory events of the intestine.

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 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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. Arimura A, Somogyvari-Vigh A, Weill C, Fiore RC, Tatsuno I, Bay V, et al. PACAP functions as a neurotrophic factor. Ann N Y Acad Sci. 1994;739:228–43.

    Article  CAS  PubMed  Google Scholar 

  2. Somogyvari-Vigh A, Reglodi D. Pituitary adenylate cyclase activating polypeptide: a potential neuroprotective peptide. Curr Pharm Des. 2004;10:2861–89.

    Article  CAS  PubMed  Google Scholar 

  3. Lee EH, Seo SR. Neuroprotective roles of pituitary adenylate cyclase-activating polypeptide in neurodegenerative diseases. BMB Rep. 2014;47:369–75.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Reglodi D, Kiss P, Lubics A, Tamas A. Review on the protective effects of PACAP in models of neurodegenerative diseases in vitro and in vivo. Curr Pharm Des. 2011;17:962–72.

    Article  CAS  PubMed  Google Scholar 

  5. Shioda S, Nakamachi T. PACAP as a neuroprotective factor in ischemic neuronal injuries. Peptides. 2015;72:202–7.

    Article  CAS  PubMed  Google Scholar 

  6. Fujimiya M, Inui A. Peptidergic regulation of gastrointestinal motility in rodents. Peptides. 2000;21:1565–82.

    Article  CAS  PubMed  Google Scholar 

  7. Holmberg A, Schwerte T, Pelster B, Holmgren S. Ontogeny of the gut motility control system in zebrafish Danio rerio embryos and larvae. J Exp Biol. 2004;207:4085–94.

    Article  PubMed  Google Scholar 

  8. Farre R, Auli M, Lecea B, Martinez E, Clave P. Pharmacologic characterization of intrinsic mechanisms controlling tone and relaxation of porcine lower esophageal sphincter. J Pharmacol Exp Ther. 2006;316:1238–48.

    Article  CAS  PubMed  Google Scholar 

  9. Lindestrom LM, Ekblad E. Origins and projections of nerve fibres in rat pyloric sphincter. Auton Neurosci. 2002;97:73–82.

    Article  PubMed  Google Scholar 

  10. Rattan S, Chakder S. Sites of actions of contractile and relaxant effects of pituitary adenylate cyclase activating peptide (PACAP) in the internal anal sphincter smooth muscle. Ann N Y Acad Sci. 1998;865:503–11.

    Article  CAS  PubMed  Google Scholar 

  11. Al-Qudah M, Alkahtani R, Akbarali HI, Murthy KS, Grider JR. Stimulation of synthesis and release of brain-derived neurotropic factor from intestinal smooth muscle cells by substance P and pituitary adenylate cyclase-activating peptide. Neurogastroenterol Motil. 2015;27:1162–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wu MJ, Kee KH, Na J, Kim SW, Bae Y, Shin DH, et al. Pituitary adenylate cyclase-activating polypeptide inhibits pacemaker activity of colonic interstitial cells of Cajal. Korean J Physiol Pharmacol. 2015;19:435–40.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ferencz A, Szanto Z, Borsiczky B, Kiss K, Kalmar-Nagy K, Telek G, et al. The effects of preconditioning on the oxidative stress in small bowel autotransplantation. Surgery. 2002;132:877–84.

    Article  PubMed  Google Scholar 

  14. Mittal A, Phillips ARJ, Loveday B, Windsor JA. The potential role for xanthine oxidase inhibition in major intra-abdominal surgery. World J Surg. 2008;32:288–95.

    Article  PubMed  Google Scholar 

  15. Reglodi D, Somogyvari-Vigh A, Vigh S, Kozicz T, Arimura A. Delayed systemic administration of PACAP38 is neuroprotective in transient middle cerebral artery occlusion in rat. Stroke. 2000;31:1411–7.

    Article  CAS  PubMed  Google Scholar 

  16. Uchida D, Arimura A, Somogyvari-Vigh A, Shioda S, Banks WA. Prevention of ischemia-induced death of hippocampal neurons by pituitary adenylate cyclase activating polypeptide. Brain Res. 1996;736:280–6.

    Article  CAS  PubMed  Google Scholar 

  17. Brifault C, Gras M, Liot D, May V, Vaudry D, Wurtz O. Delayed pituitary adenylate cyclase-activating polypeptide delivery after brain stroke improves functional recovery by inducing m2 microglia/macrophage polarization. Stroke. 2015;46:520–8.

    Article  CAS  PubMed  Google Scholar 

  18. Chen Y, Samal B, Hamelink CR, Xiang CC, Chen Y, Chen M, et al. Neuroprotection by endogenous and exogenous PACAP following stroke. Regul Pept. 2006;137:4–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lenti L, Zimmermann A, Kis D, Olah O, Toth GK, Hegyi O, et al. PACAP and VIP differentially preserve neurovascular reactivity after global cerebral ischemia in newborn pigs. Brain Res. 2009;1283:50–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tamas A, Reglodi D, Szanto Z, Borsiczky B, Nemeth J, Lengvari I. Comparative neuroprotective effects of preischemic PACAP and VIP administration in permanent occlusion of the middle cerebral artery in rats. Neuro Endocrinol Lett. 2002;23:249–54.

    CAS  PubMed  Google Scholar 

  21. Atlasz T, Szabadfi K, Kiss P, Tamas A, Toth G, Reglodi D, et al. Evaluation of the protective effects of PACAP with cell-specific markers in ischemia-induced retinal degeneration. Brain Res Bull. 2010;81:497–504.

    Article  CAS  PubMed  Google Scholar 

  22. Danyadi B, Szabadfi K, Reglodi D, Mihalik A, Danyadi T, Kovacs Z, et al. PACAP application improves functional outcome of chronic retinal ischemic injury in rats-evidence from electroretinographic measurements. J Mol Neurosci. 2014;54:293–9.

    Article  CAS  PubMed  Google Scholar 

  23. Seki T, Itoh H, Nakamachi T, Endo K, Wada Y, Nakamura K, et al. Suppression of rat retinal ganglion cell death by PACAP following transient ischemia induced by high intraocular pressure. J Mol Neurosci. 2011;43:30–4.

    Article  CAS  PubMed  Google Scholar 

  24. Ji H, Zhang Y, Shen XD, Gao F, Huang CY, Abad C, et al. Neuropeptide PACAP in mouse liver ischemia and reperfusion injury: immunomodulation by the cAMP-PKA pathway. Hepatology. 2013;57:1225–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Horvath G, Racz B, Reglodi D, Kovacs K, Kiss P, Gallyas Jr F, et al. Effects of PACAP on mitochondrial apoptotic pathways and cytokine expression in rats subjected to renal ischemia/reperfusion. J Mol Neurosci. 2010;42:411–8.

    Article  CAS  PubMed  Google Scholar 

  26. Laszlo E, Kiss P, Horvath G, Szakaly P, Tamas A, Reglodi D. The effects of pituitary adenylate cyclase-activating polypeptide in renal ischemia/reperfusion. Acta Biol Hung. 2014;65:369–78.

    Article  CAS  PubMed  Google Scholar 

  27. Laszlo E, Varga A, Kovacs K, Jancso G, Kiss P, Tamas A, et al. Ischemia/reperfusion-induced kidney injury in heterozygous PACAP-deficient mice. Transplant Proc. 2015;47:2210–5.

    Article  CAS  PubMed  Google Scholar 

  28. Szakaly P, Kiss P, Lubics A, Magyarlaki T, Tamas A, Racz B, et al. Effects of PACAP on survival and renal morphology in rats subjected to renal ischemia/reperfusion. J Mol Neurosci. 2008;36:89–96.

    Article  CAS  PubMed  Google Scholar 

  29. Roth E, Weber G, Kiss P, Horvath G, Toth G, Gasz B, et al. Effect of PACAP and preconditioning against ischemia/reperfusion-induced cardiomyocyte apoptosis in vitro. Ann N Y Acad Sci. 2009;1163:512–6.

    Article  CAS  PubMed  Google Scholar 

  30. Ferencz A, Racz B, Tamas A, Reglodi D, Lubics A, Nemeth J, et al. Influence of PACAP on oxidative stress and tissue injury following small-bowel autotransplantation. J Mol Neurosci. 2009;37:168–76.

    Article  CAS  PubMed  Google Scholar 

  31. Ferencz A, Racz B, Tamas A, Nedvig K, Nemeth J, Kalmar-Nagy K, et al. Changes and effect of PACAP-38 on intestinal ischemia-reperfusion and autotransplantation. Transplant Proc. 2009;41:57–9.

    Article  CAS  PubMed  Google Scholar 

  32. Ferencz A, Reglodi D, Kalmar-Nagy K, Horvath OP, Roth E, Weber G, et al. Influence of pituitary adenylate cyclase-activating polypeptide on the activation of mitogen activated protein kinases following small bowel cold preservation. Transplant Proc. 2009;41:60–2.

    Article  CAS  PubMed  Google Scholar 

  33. Nedvig K, Weber G, Nemeth J, Kovacs K, Reglodi D, Kemeny A, et al. Changes of PACAP immunoreactivities and cytokine levels after PACAP-38 containing intestinal preservation and autotransplantation. J Mol Neurosci. 2012;48:788–94.

    Article  CAS  PubMed  Google Scholar 

  34. Seaborn T, Masmoudi-Kouli O, Fournier A, Vaudry H, Vaudry D. Protective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) against apoptosis. Curr Pharm Des. 2011;17:204–14.

    Article  CAS  PubMed  Google Scholar 

  35. Brown D, Tamas A, Reglodi D, Tizabi Y. PACAP protects against inflammatory-mediated toxicity in dopaminerg SH-SY5Y cells: implication for Parkinson’s disease. Neurotox Res. 2014;26:230–9.

    Article  CAS  PubMed  Google Scholar 

  36. Dejda A, Seaborn T, Bourgault S, Touzani O, Fournier A, Vaudry H, et al. PACAP and a novel stable analog protect rat brain from ischemia: insight into the mechanisms of action. Peptides. 2011;32:1207–16.

    Article  CAS  PubMed  Google Scholar 

  37. Rozzi SJ, Borelli G, Ryan K, Steiner JP, Reglodi D, Mocchetti I, et al. PACAP27 is protective against tat-induced neurotoxicity. J Mol Neurosci. 2014;54:485–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Racz B, Horvath G, Reglodi D, Gasz B, Kiss P, Gallyas Jr F, et al. PACAP ameliorates oxidative stress in the chicken inner ear: an in vitro study. Regul Pept. 2010;160:91–8.

    Article  CAS  PubMed  Google Scholar 

  39. Szabadfi K, Szabo A, Kiss P, Reglodi D, Setalo Jr G, Kovacs K, et al. PACAP promotes neuron survival in early experimental diabetic retinopathy. Neurochem Int. 2014;64:84–91.

    Article  CAS  PubMed  Google Scholar 

  40. Banki E, Kovacs K, Nagy D, Juhasz T, Degrell P, Csanaky K, et al. Molecular mechanisms underlying the nephroprotective effects of PACAP in diabetes. J Mol Neurosci. 2014;54:300–9.

    Article  CAS  PubMed  Google Scholar 

  41. Gasz B, Racz B, Roth E, Borsiczky B, Ferencz A, Tamas A, et al. Pituitary adenylate cyclase-activating polypeptide protects cardiomyocytes against oxidative stress-induced apoptosis. Peptides. 2006;27:87–94.

    Article  CAS  PubMed  Google Scholar 

  42. Mori H, Nakamachi T, Ohtaki H, Yofu S, Sato A, Endo K, et al. Cardioprotective effect of endogenous pituitary adenylate cyclase-activating polypeptide on doxorubicin-induced cardiomyopathy in mice. Circ J. 2010;74:1183–90.

    Article  CAS  PubMed  Google Scholar 

  43. Miyamoto K, Tsumuraya T, Ohtaki H, Dohi K, Satoh K, Xu Z, et al. PACAP38 suppresses cortical damage in mice with traumatic brain injury by enhancing antioxidant activity. J Mol Neurosci. 2014;54:370–9.

    Article  CAS  PubMed  Google Scholar 

  44. Masmoudi-Kouki O, Douiri S, Hamdi Y, Kaddour H, Bahdoudi S, Vaudry D, et al. Pituitary adenylate cyclase-activating polypeptide protects astroglial cells against oxidative stress-induced apoptosis. J Neurochem. 2011;117:403–11.

    Article  CAS  PubMed  Google Scholar 

  45. Horvath G, Brubel R, Kovacs K, Reglodi D, Opper B, Ferencz A, et al. Effects of PACAP on oxidative stress-induced cell death in rat kidney and human hepatocyte cells. J Mol Neurosci. 2011;43:67–75.

    Article  CAS  PubMed  Google Scholar 

  46. Reglodi D, Fabian Z, Tamas A, Lubics A, Szeberenyi J, Alexy T, et al. Effects of PACAP on in vitro and in vivo neuronal cell death, platelet aggregation, and production of reactive oxygen radicals. Regul Pept. 2004;123:51–9.

    Article  CAS  PubMed  Google Scholar 

  47. Delgado M, Genea D. Inhibition of endotoxin-induced macrophage chemokine production by vasoactive intestinal peptide and pituitary adenylate cyclise activating polypeptide in vitro and in vivo. J Immunol. 2001;167:966–75.

    Article  CAS  PubMed  Google Scholar 

  48. Abad C, Waschek JA. Immunomodulatory roles of VIP and PACAP in models of multiple sclerosis. Curr Pharm Des. 2011;17:1025–35.

    Article  CAS  PubMed  Google Scholar 

  49. Ganea D, Rodriguez R, Delgado M. Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: players in innate and adaptive immunity. Cell Mol Biol (Noisy-le-grand). 2003;49:127–42.

    CAS  Google Scholar 

  50. Delgado M, Jonakait GM, Ganea D. Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit chemokine production in activated microglia. Glia. 2002;39:148–61.

    Article  PubMed  Google Scholar 

  51. Delgado M, Leceta J, Ganea D. Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit the production of inflammatory mediators by activated microglia. J Leukoc Biol. 2003;73:155–64.

    Article  CAS  PubMed  Google Scholar 

  52. Wainwright DA, Xin J, Sanders VM, Jones KJ. Differential actions of pituitary adenylyl cyclase-activating polypeptide and interferon gamma on Th2- and Th1-associated chemokine expression in cultured murine microglia. J Neurodegener Regen. 2008;1:31–4.

    PubMed  PubMed Central  Google Scholar 

  53. Wada Y, Nakamachi T, Endo K, Seki T, Ohtaki H, Tsuchikawa D, et al. PACAP attenuates NMDA-induced retinal damage in association with modulation of the microglia/macrophage status into an acquired deactivation subtype. J Mol Neurosci. 2013;51:493–502.

    Article  CAS  PubMed  Google Scholar 

  54. Banki E, Degrell P, Kiss P, Kovacs K, Kemeny A, Csanaky K, et al. Effect of PACAP treatment on kidney morphology and cytokine expression in rat diabetic nephropathy. Peptides. 2013;42:125–30.

    Article  CAS  PubMed  Google Scholar 

  55. Szabo A, Danyadi B, Bognar E, Szabadfi K, Fabian E, Kiss P, et al. Effect of PACAP on MAP kinases, Akt and cytokine expressions in rat retinal hypoperfusion. Neurosci Lett. 2012;523:93–8.

    Article  CAS  PubMed  Google Scholar 

  56. Ferencz A, Weber G, Helyes Z, Hashimoto H, Baba A, Reglodi D. Presence of endogenous PACAP-38 ameliorated intestinal cold preservation tissue injury. J Mol Neurosci. 2010;42:428–34.

    Article  CAS  PubMed  Google Scholar 

  57. Ferencz A, Kiss P, Weber G, Helyes Z, Shintani N, Baba A, et al. Comparison of intestinal warm ischemic injury in PACAP knockout and wild-type mice. J Mol Neurosci. 2010;42:435–42.

    Article  CAS  PubMed  Google Scholar 

  58. Ferencz A, Nedvig K, Fekecs T, Racz B, Weber G, Hashimoto H, et al. Comparison of intestinal cold preservation injury on pituitary adenylate cyclase-activating polypeptide in knockout and wild-type mice. Transplant Proc. 2010;42:2290–2.

    Article  CAS  PubMed  Google Scholar 

  59. Reglodi D, Kiss P, Szabadfi K, Atlasz T, Gabriel R, Horvath G, et al. PACAP is an endogenous protective factor-insights from PACAP-deficient mice. J Mol Neurosci. 2012;48:482–92.

    Article  CAS  PubMed  Google Scholar 

  60. Ohtaki H, Nakamachi T, Dohi K, Aizawa Y, Takaki A, Hodoyama K, et al. Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6. Proc Natl Acad Sci U S A. 2006;103:7488–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Nakamachi T, Ohtaki H, Yofu S, Dohi K, Watanabe J, Mori H, et al. Endogenous pituitary adenylate cyclase activating polypeptide is involved in suppression of edema in the ischemic brain. Acta Neurochir Suppl. 2010;106:43–6.

    Article  PubMed  Google Scholar 

  62. Szabadfi K, Atlasz T, Kiss P, Danyadi B, Tamas A, Helyes Z, et al. Mice deficient in pituitary adenylate cyclase-activating polypeptide (PACAP) are more susceptible to retinal ischemic injury in vivo. Neurotox Res. 2012;21:41–8.

    Article  CAS  PubMed  Google Scholar 

  63. Szakaly P, Laszlo E, Kovacs K, Racz B, Horvath G, Ferencz A, et al. Mice deficient in pituitary adenylate cyclase activating polypeptide (PACAP) show increased susceptibility to in vivo renal ischemia/reperfusion injury. Neuropeptides. 2011;45:113–21.

    Article  CAS  PubMed  Google Scholar 

  64. Elekes K, Sandor K, Moricz A, Kereskai L, Kemeny A, Szoke E, et al. Pituitary adenylate cyclase-activating polypeptide plays an anti-inflammatory role in endotoxin-induced airway inflammation: In vivo study with gene-deleted mice. Peptides. 2011;32:1439–46.

    Article  CAS  PubMed  Google Scholar 

  65. Kemeny A, Reglodi D, Cseharovszky R, Hashimoto H, Baba A, Szolcsanyi J, et al. Pituitary adenylate cyclase-activating polypeptide deficiency enhances oxazolone-induced allergic contact dermatitis in mice. J Mol Neurosci. 2010;42:443–9.

    Article  CAS  PubMed  Google Scholar 

  66. Maasz G, Pirger Z, Reglodi D, Petrovics D, Schmidt J, Kiss P, et al. Comparative protein composition of the brains of PACAP-deficient mice using mass spectrometry-based proteomic analysis. J Mol Neurosci. 2014;54:310–9.

    Article  CAS  PubMed  Google Scholar 

  67. Watson MB, Nobuta H, Abad C, Lee SK, Bala N, Zhu C, et al. PACAP deficiency sensitizes nigrostriatal dopaminergic neurons to paraquat-induced damage and modulates central and peripheral inflammatory activation in mice. Neuroscience. 2013;240:277–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;19:2066–78.

    Article  Google Scholar 

  69. Ekelund M, Ekblad E. Intestinal adaptation in atrophic rat ileum is accompanied by supersensitivity to vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide and nitric oxide. Scand J Gastroenterol. 2001;36:251–7.

    Article  CAS  PubMed  Google Scholar 

  70. Lazar Z, Shahbazian A, Benko R, Toth G, Penke B, Bartho L, et al. PACAP-(6-38) inhibits the effects of vasoactive intestinal polypeptide, but not PACAP, on the small intestinal circular muscle. Eur J Pharmacol. 2001;431:259–64.

    Article  CAS  PubMed  Google Scholar 

  71. Mao YK, Wang YF, Moogk C, Fox-Threlkeld JE, Xiao Q, McDonald TJ, et al. Locations and molecular forms of PACAP and sites and characteristics of PACAP receptors in canine ileum. Am J Physiol. 1998;274:G217–25.

    CAS  PubMed  Google Scholar 

  72. Pirone A, Baoan D, Piano I, Della Santina L, Baglini A, Lenzi C. Pituitary adenylate cyclase-activating peptide (PACAP) immunoreactivity distribution in the small intestine of the adult New Hampshire chicken. Acta Histochem. 2011;113:477–83.

    Article  CAS  PubMed  Google Scholar 

  73. Zizzo MG, Mulé F, Serio R. Mechanisms underlying the inhibitory effects induced by pituitary adenylate cyclase-activating peptide in mouse ileum. Eur J Pharmacol. 2005;521:133–8.

    Article  CAS  PubMed  Google Scholar 

  74. Belai A, Boulos PB, Robson T, Burnstock G. Neurochemical coding in the small intestine of patients with Crohn's disease. Gut. 1997;40:767–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. He CL, Soffer EE, Ferris CD, Walsh RM, Szurszewski JH, Farrugia G. Loss of interstitial cells of cajal and inhibitory innervation in insulin-dependent diabetes. Gastroenterology. 2001;121:427–34.

    Article  CAS  PubMed  Google Scholar 

  76. Heimesaat MM, Dunay IR, Schulze S, Fischer A, Grundmann U, Alutis M, et al. Pituitary adenylate cyclase-activating polypeptide ameliorates experimental acute ileitis and extra-intestinal sequelae. PLoS One. 2014;9:e108389.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Leung PS, So SC, Lam SY, Tsang LL, Chung YW, Chan HC. Local regulation of anion secretion by pituitary adenylate cyclase-activating polypeptide in human colonic T84 cells. Cell Biol Int. 2001;25:123–9.

    Article  CAS  PubMed  Google Scholar 

  78. Rettenbacher M, Reubi JC. Localization and characterization of neuropeptide receptors in human colon. Naunyn Schmiedebergs Arch Pharmacol. 2001;364:291–304.

    Article  CAS  PubMed  Google Scholar 

  79. Miampamba M, Germano PM, Arli S, Wong HH, Scott D, Tache Y, et al. Expression of pituitary adenylate cyclase-activating polypeptide and PACAP type 1 receptor in the rat gastric and colonic myenteric neurons. Regul Pept. 2002;105:145–54.

    Article  CAS  PubMed  Google Scholar 

  80. Uyttebroek L, Shepherd IT, Harrisson F, Hubens G, Blust R, Timmermans JP, et al. Neurochemical coding of enteric neurons in adult and embryonic zebrafish (Danio rerio). Cancer Res. 2012;72:1705–16.

    Article  Google Scholar 

  81. Gonkowski S, Calka J. Changes in pituitary adenylate cyclase-activating peptide 27-like immunoreactive nervous structures in the porcine descending colon during selected pathological processes. J Mol Neurosci. 2012;48:777–87.

    Article  CAS  PubMed  Google Scholar 

  82. Gonkowski S, Kaminska B, Landowski P, Calka J. Immunohistochemical distribution of cocaine- and amphetamine-regulated transcript peptide-like immunoreactive (CART-LI) nerve fibers and various degree of co-localization with other neuronal factors in the circular muscle layer of human descending colon. Histol Histopathol. 2013;28:851–8.

    PubMed  Google Scholar 

  83. Wojtkiewicz J, Rowniak M, Gonkowski S, Crayton R, Majewski M, Robak A, et al. Proliferative enteropathy (PE)-induced changes in the calbindin-immunoreactive (CB-IR) neurons of inferior mesenteric ganglion supplying the descending colon in the pig. J Mol Neurosci. 2012;48:757–65.

    Article  CAS  PubMed  Google Scholar 

  84. Kun J, Szitter I, Kemeny A, Perkecz A, Kereskai L, Pohoczky K, et al. Upregulation of the transient receptor potential ankyrin 1 ion channel in the inflamed human and mouse colon and its protective roles. PLoS One. 2014;9:e108164.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Vinuesa AG, Sancho R, Garcia-Limones C, Behrens A, Ten Dijke P, Calzado MA, et al. Vanilloid receptor-1 regulates neurogenic inflammation in colon and protects mice from colon cancer. J Comp Neurol. 2010;518:4419–38.

    Article  Google Scholar 

  86. Szanto Z, Sarszegi Z, Reglodi D, Nemeth J, Szabadfi K, Kiss P, et al. PACAP immunoreactivity in human malignant tumor samples and cardiac diseases. J Mol Neurosci. 2012;48:667–73.

    Article  CAS  PubMed  Google Scholar 

  87. Tamas A, Javorhazy A, Reglodi D, Sarlos DP, Banyai D, Semjen D, et al. Examination of PACAP-like immunoreactivity in urogenital tumor samples. J Mol Neurosci. 2016;59:177–83.

    Google Scholar 

  88. Godlewski J, Lakomy IM. Changes in vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide and neuropeptide Y-ergic structures of the enteric nervous system in the carcinoma of the human large intestine. Folia Histochem Cytobiol. 2010;48:208–16.

    PubMed  Google Scholar 

  89. Simpson J, Sundler F, Humes DJ, Jenkins D, Scholefield JH, Spiller RC. Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptoms. Neurogastroenterol Motil. 2009;21:847–e58.

    Article  CAS  PubMed  Google Scholar 

  90. Kaminska B, Landowski P, Gonkowski S, Majewski M, Renke J, Korzon M. Changes in the number of neuroprotective transmitter containing mucosal nerve fibres in children with ulcerative colitis. Med Wieku Rozwoj. 2006;10:483–91.

    PubMed  Google Scholar 

  91. Kaminska B, Landowski P, Gonkowski S, Szlagatys-Sidorkiewitz A, Majewski M, Dobosz M, et al. Analysis of enteral nervous system in children with drug resistant ulcerative colitis. Med Wieku Rozwoj. 2007;11:117–22.

    PubMed  Google Scholar 

  92. Shen Z, Larsson LT, Malmfors G, Absood A, Håkanson R, Sundler F. A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in human intestine: evidence for reduced content in Hirschsprung's disease. Cell Tissue Res. 1992;269:369–74.

    Article  CAS  PubMed  Google Scholar 

  93. Jakab B, Reglodi D, Jozsa R, Hollosy T, Tamas A, Lubics A, et al. Distribution of PACAP-38 in the central nervous system of various species determined by a novel radioimmunoassay. J Biochem Biophys Methods. 2004;61:189–98.

    Article  CAS  PubMed  Google Scholar 

  94. Nemeth J, Jakab B, Jozsa R, Hollosy T, Tamas A, Lubics A, et al. PACAP-27 radioimmunoassay: description and application of a novel method. J Radioanal Nucl Chem. 2007;273:327–32.

    Article  CAS  Google Scholar 

  95. Azuma YT, Hagi K, Shintani N, Kuwamura M, Nakajima H, Hashimoto H, et al. PACAP provides colonic protection against dextran sodium sulfate induced colitis. J Cell Physiol. 2008;216:111–9.

    Article  CAS  PubMed  Google Scholar 

  96. Nemetz N, Abad C, Lawson G, Nobuta H, Chhith S, Doung L, et al. Induction of colitis and rapid development of colorectal tumors in mice deficient in the neuropeptide PACAP. Int J Cancer. 2008;122:1803–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by OTKA K104984, 119759 Arimura Foundation, TAMOP 4.2.4.A/2-11-1-2012-0001 “National Excellence Program,” Bolyai Scholarship of the Hungarian Academy of Sciences, PTE AOK KA Research Grant, PTE-KA 300019 and New National Excellence Program (UNKP). This work is dedicated to the 650th anniversary of the University of Pecs.

Author information

Author notes

    Authors and Affiliations

    1. Department of Anatomy, MTA-PTE “Lendulet” PACAP Research Group, University of Pecs, Pecs, Hungary

      Gabriella Horvath, Anita Illes, Andrea Tamas, Balazs D. Fulop, Balazs Opper & Dora Reglodi M.D., Ph.D.

    2. Department of Internal Medicine, University of Pecs, Pecs, Hungary

      Anita Illes

    3. Department of Microbiology and Hygiene, Charite-University Medicine, Berlin, Germany

      Markus M. Heimesaat

    4. Jakob Henle Institute for Pathology and Neuropathology, Limbach Group, Heidelberg, Germany

      Attila Bardosi & Sebastian Bardosi

    5. Department of Pharmacology and Pharmacotherapy, University of Debrecen, Debrecen, Hungary

      Jozsef Nemeth

    6. Department of Surgical Research and Techniques, Semmelweis University, Budapest, Hungary

      Andrea Ferencz

    Authors
    1. Gabriella Horvath
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Anita Illes
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Markus M. Heimesaat
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Attila Bardosi
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Sebastian Bardosi
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Andrea Tamas
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Balazs D. Fulop
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Balazs Opper
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Jozsef Nemeth
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Andrea Ferencz
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Dora Reglodi M.D., Ph.D.
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Dora Reglodi M.D., Ph.D. .

    Editor information

    Editors and Affiliations

    1. Department of Anatomy MTA-PTE “Lendulet” PACAP Research Team, University of Pecs, Pecs, Hungary

      Dora Reglodi

    2. Department of Anatomy MTA-PTE “Lendulet” PACAP Research Team, University of Pecs, Pecs, Hungary

      Andrea Tamas

    Rights and permissions

    Reprints and permissions

    Copyright information

    © 2016 Springer International Publishing Switzerland

    About this chapter

    Cite this chapter

    Horvath, G. et al. (2016). Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide. In: Reglodi, D., Tamas, A. (eds) Pituitary Adenylate Cyclase Activating Polypeptide — PACAP. Current Topics in Neurotoxicity, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-319-35135-3_17

    Download citation

    Publish with us

    Policies and ethics

    Search

    Navigation