Skip to main content
SpringerLink
Log in

Biological Oxidants as Intestinal Secretagogues

  • Chapter
Biochemical Pharmacology as an Approach to Gastrointestinal Disorders

  • 117 Accesses

Abstract

Inflammatory bowel disease (IBD) is associated with the release by granulocytes of a variety of oxidants. These oxidants include hydrogen peroxide, hypochlorous acid, superoxide radicals and nitrogen-containing compounds, such as N-chloramines and nitric oxide and its metabolites. In-vivo experiments and clinical observations suggest that some or all of these oxidants may be involved in the pathophysiology of the diarrhoea that is a hallmark symptom of IBD. In vitro, all of these oxidants stimulate to varying degrees small intestinal and/or colonic electrolyte secretion. This chapter will focus principally on the action of monochloramine (formed from hypochlorous acid and ammonia) and nitric oxide (NO). Evidence is presented to support the idea that these oxidants act through direct and indirect mechanisms in the mucosa to stimulate electrolyte secretion. This may contribute to the accumulation of fluid in the intestine of patients with IBD and contribute to diarrhoea. NO is intriguing because it may physiologically stimulate absorption yet, at higher concentrations, stimulate secretion (as in IBD) and be involved in the diarrhoeagenic action of several laxatives.

Correspondence

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 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Gaginella TS, Kachur JF, Tamai H, Keshavarzian A. Reactive oxygen and nitrogen metabolites as mediators of secretory diarrhea. Gastroenterology. 1995; 109: 2019–28.

    Article  PubMed  CAS  Google Scholar 

  2. Caprilli R, Sopranzi N, Colaneri O. Salt losing diarrhea in idiopathic proctocolitis. Scand J Gastroenterol. 1978; 13: 331–5.

    Article  PubMed  CAS  Google Scholar 

  3. Schilli R, Brueur RI, Klein F. A comparison of the composition of fecal fluid in Crohn’s disease and ulcerative colitis. Gut. 1982; 23: 326–32.

    Article  PubMed  CAS  Google Scholar 

  4. Smiddy FG, Gregory SD, Smith IB, Goligher JC. Faecal loss of fluid, electrolytes and nitrogen in colitis before and after ileostomy. Lancet. 1960; 1: 14–19.

    Article  PubMed  CAS  Google Scholar 

  5. Harris J, Shields R. Absorption and secretion of water and electrolytes by the intact human colon in diffuse untreated proctocolitis. Gut. 1970; 11: 27–33.

    Article  PubMed  CAS  Google Scholar 

  6. Head LH, Heaton JW Jr, Kivel RM. Absorption of water and electrolytes in Crohn’s disease of the colon. Gastroenterology. 1969; 56: 571–9.

    PubMed  CAS  Google Scholar 

  7. Jenkins RT, Goodacre RL, Rooney PJ, Bienenstock J, Sivakumaran J, Walker WHC. Studies of intestinal permeability in inflammatory diseases using polyethylene glycol 400. Clin Biochem. 1986; 19: 298–302.

    Article  PubMed  CAS  Google Scholar 

  8. Ukabam SO, Clamp JR, Cooper BT. Abnormal small intestinal permeability to sugars in patients with Crohn’s disease of the terminal ileum and colon. Digestion. 1982; 27: 70–4.

    Article  Google Scholar 

  9. Bjarnasson I, O’Morain C, Levi AJ, Peters AJ. Absorption of 51chromium-labeled ethylenediaminetetraacetate in inflammatory bowel disease. Gastroenterology. 1983; 85: 318–22.

    Google Scholar 

  10. Rachmilewitz D, Karmeli F, Sharon P. Decreased colonic Na-K-ATPase activity in active ulcerative colitis. Israel 7 Med Sci. 1984; 20: 681–4.

    CAS  Google Scholar 

  11. Kachur JF, Keshavarzian A, Sundaresan R et al. Colitis reduces the short-circuit response to inflammatory mediators in rat colonic mucosa. Inflammation. 1995; 19: 245–59.

    Article  PubMed  CAS  Google Scholar 

  12. Goldhill J, Zhao L, Xu Y, Donovan V, Burakoff R. Defective stimulation of cyclic AMP by prostaglandin E2 in colonic epithelial cells in colitis. Eur J Pharmacol. 1993; 238: 387–90.

    Article  PubMed  CAS  Google Scholar 

  13. Goldhill JM, Burakoff R, Donovan V, Rose K, Percy WH. Defective modulation of colonic secretamotor neurons in a rabbit model of colitis. Am J Physiol. 1993; 264: G671–7.

    PubMed  CAS  Google Scholar 

  14. Yamada T, Grisham MB. Pathogenesis of tissue injury: role of reactive metabolites of oxygen and nitrogen. In: Targan SR, Shanahan F, eds. Inflammatory Bowel Disease from Bench to Bedside. Baltimore: Williams and Wilkins; 1994: 133–50.

    Google Scholar 

  15. Miller MJS, Gaginella TS. Nitric oxide as a mediator of mucosal function. In: Gaginella TS, ed. Regulatory Mechanisms in Gastrointestinal Pharmacology. Boca Raton: CRC Press. 1995: 199–218.

    Google Scholar 

  16. Rachmilewitz D, Stamler JSJ, Karmeli F et al. Peroxynitrite-induced rat colitis–a new model of colonic inflammation. Gastroenterology. 1993; 105: 1681–8.

    PubMed  CAS  Google Scholar 

  17. Beckman JSJ, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA. 1990; 87: 1620–4.

    Article  PubMed  CAS  Google Scholar 

  18. Halliwell B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet. 1994; 344: 721–4.

    Article  PubMed  CAS  Google Scholar 

  19. Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys. 1991; 288: 481–7.

    Article  PubMed  CAS  Google Scholar 

  20. Gaginella TS. Receptor pharmacology of intestinal secretion. In: Lebenthal E, Duffey M, eds. Secretory Diarrhea. New York, NY: Raven Press; 1990: 163–78.

    Google Scholar 

  21. Gaginella TS, Kachur JF. Kinins as mediators of intestinal secretion. Am J Physiol. 1989; 256: G1 - G15.

    PubMed  CAS  Google Scholar 

  22. Gaginella TS. Eicosanoid-mediated intestinal secretion. In: Lebenthal E, Duffey M, eds. Secretory Diarrhea. New York, NY: Raven Press; 1990: 15–30.

    Google Scholar 

  23. Gaginella TS. Absorption and secretion in the colon. Curr Opin Gastroenterol. 1995; 11: 2–8.

    Article  Google Scholar 

  24. Karayalcin SS, Sturbaum CW, Wachsman JT, Cha J-H, Powell DW. Hydrogen peroxide stimulates rat colonic prostaglandin production and alters electrolyte transport. Clin Invest. 1990; 86: 60–8.

    Article  CAS  Google Scholar 

  25. Tamai H, Kachur JF, Baron DA, Grisham MB, Gaginella TS. Monochloramine, a neutrophil-derived oxidant, stimulates rat colonic secretion. J Pharmacol Exp Ther. 1991; 257: 887–94.

    PubMed  CAS  Google Scholar 

  26. Bern MJ, Ssturbaum CW, Karayalcin SS, Bernschneider HM, Wachsman JT, Powell DW. Immune system control of rat and rabbit colonic electrolyte transport: Role of prostaglandins and enteric nervous system. J Clin Invest. 1988; 83: 1810–20.

    Article  Google Scholar 

  27. Gaginella TS, Grisham MB, Thomas DB, Walsh R, Moummi C. Oxidant-evoked release of acetylcholine from enteric neurons of the rat colon. J Pharmacol Exp Ther. 1992; 263: 1068–73.

    PubMed  CAS  Google Scholar 

  28. Donowitz M. Arachidonic acid metabolites and their role in inflammatory bowel disease: An update requiring addition of a pathway. Gastroenterology. 1985; 85: 50–587.

    Google Scholar 

  29. Tamai H, Gaginella TS, Kachur JF, Musch MW, Chang EB. Ca-mediated stimulation of Cl secretion by reactive oxygen metabolites in human colonic T84 cells. J Clin Invest. 1992; 89: 301–7.

    Article  PubMed  CAS  Google Scholar 

  30. Grisham MB, Gaginella TS, von Ritter C, Tamai H, Be RM, Granger DN. Effects of neutrophilderived oxidants on intestinal permeability, electrolyte transport, and epithelial cell viability. Inflammation. 1990; 14: 531–42.

    Article  PubMed  CAS  Google Scholar 

  31. Tamai H, Kachur JF, Grisham MB, Musch MW, Chang EB, Gaginella TS. Effect of the thiol-oxidizing agent diamide on NH2C1-induced rat colonic electrolyte secretion. Am J Physiol. 1993;265:C166–70.

    PubMed  CAS  Google Scholar 

  32. Thomas DD, Knoop FC. The effect of calcium and prostaglandin inhibitors on the intestinal fluid response to heat-stable enterotoxin of Escherichia coli. J Infect Dis. 1982; 145: 141–5.

    Article  PubMed  CAS  Google Scholar 

  33. Wilson KT, Xie Y, Musch MW, Chang EB. Sodium nitroprusside stimulates anion secretion and inhibits sodium chloride absorption in rat colon. J Pharmacol Exp Ther. 1993; 266: 224–30.

    PubMed  CAS  Google Scholar 

  34. MacNaughton WK. Nitric oxide-donating compounds stimulate electrolyte transport in the guinea pig intestine in vitro. Life Sci. 1993; 53: 585–93.

    Article  PubMed  CAS  Google Scholar 

  35. Tamai H, Gaginella TS. Direct evidence for nitric oxide stimulation of electrolyte secretion in the rat colon. Free Rad Res Commun. 1993; 19: 229–39.

    Article  CAS  Google Scholar 

  36. Mascolo N, Izzo AA, Barbato F, Capasso F. Inhibitors of nitric oxide synthetase prevent castor-oil-induced diarrhoea in the rat. Br J Pharmacol. 1993; 108: 861–4.

    Article  PubMed  CAS  Google Scholar 

  37. Mascolo N, Gaginella TS, Izzo AA, DiCarlo G, Capasso F. Nitric oxide involvement in sodium choleate-induced fluid secretion and diarrhoea in rats. Eur J Phannacol. 1994; 264: 21–6.

    Article  CAS  Google Scholar 

  38. Capasso F, Mascolo N, Izzo AA, Gaginella TS. Dissociation of castor-oil-induced diarrhea and intestinal mucosal injury in rat: effect of NG-nitro-L-arginine methylester. Br J Pharmacol. 1994; 113: 1127–30.

    Article  PubMed  CAS  Google Scholar 

  39. Gaginella TS, Mascolo N, Izzo AA, Autore G, Capasso F. Nitric oxide as a mediator of bisacodyl and phenolphthalein laxative action: induction of nitric oxide synthase. J Pharmacol Exp Ther. 1994; 270: 1239–45.

    PubMed  CAS  Google Scholar 

  40. Izzo A, Gaginella TS, Mascolo N, Cappasso F. Nitric oxide as a mediator of the laxative action of magnesium sulphate. 1994; 113: 228–32.

    CAS  Google Scholar 

  41. Murad F, Mittal CK, Arnold WP, Katsuki S, Kimura H. Guanylate cyclase: activation by azide, nitro compounds, nitric oxide, and hydroxyl radical and inhibition by hemoglobin and myoglobin. In: George WJ, Ignarro LJ, eds. Advances in Cyclic Nucleotide Research. New York: Raven Press, 1978.

    Google Scholar 

  42. Schmidt HHHW. NO, CO and OH endogenous soluble guanylate cyclase-activating factors. Fed Eur Biochem Soc. 1992; 307: 102–7.

    Article  Google Scholar 

  43. Arnold WP, Mittal CK, Katsuki S, Murad F. Nitric oxide activates guanylate cyclase and increases guanosine 3’:5’-cyclic monophosphate levels in various tissue preparations. Proc Nat ’ Acad Sci USA. 1977; 74: 3203–7.

    Article  CAS  Google Scholar 

  44. DeJonge HR. The localization of guanylate cyclases in rat small intestinal epithelium. FEBS Lett. 1975; 53: 237–42.

    Article  CAS  Google Scholar 

  45. Craven PA, DeRubertis FR. Cyclic nucleotide metabolism in rat colonic epithelial cells with different proliferative activities. Biochem Biophys Acta. 1981; 676: 155–69.

    Article  PubMed  CAS  Google Scholar 

  46. Currie MG, Fok KF, Kato J et al. Guanylin: an endogenous activator of intestinal guanylate cyclase. Proc Nat! Acad Sci USA. 1992; 89: 947–51.

    Article  CAS  Google Scholar 

  47. Forte LR, Eber SL, Turner JT, Freeman RH, Fok KF, Currie MG. Guanylin stimulation of Cl-secretion in human intestinal T84 cells via cyclic guanosine monophosphate. J Clin Invest. 1993; 91: 2423–8.

    Article  PubMed  CAS  Google Scholar 

  48. Wiegand RC, Kato J, Huang MD, Fok KF, Kachur JF, Currie MG. Human guanylin: cDNA isolation, structure and activity. FEBS Lett. 1992; 311: 150–154.

    Article  PubMed  CAS  Google Scholar 

  49. Guandalini S, Migliavacca M, de Campora E, Rubino A. Cyclic guanosine monophosphate effects on nutrient and electrolyte transport in rabbit ileum. Gastroenterology. 1982; 83: 15–21.

    PubMed  CAS  Google Scholar 

  50. Brasitus TA, Field M, Kimberg DV. Intestinal mucosal cyclic GMP: regulation and relation to ion transport. Am J Physiol. 1976; 231: G275–82.

    Google Scholar 

  51. Schirgi-Degen A, Beubler E. Significance of nitric oxide in the regulation of intestinal fluid transport in the rat jejunum in vivo. Gastroenterology. 1992;106:A269.

    Google Scholar 

  52. Miller MJS, Sadowska-Krowicka H, Chotinaruemol S, Kakkis JL, Clark DA. Amelioration of chronic ileitis by nitric oxide synthase inhibition. J Pharmacol Exp Ther. 1993;264:11–16.

    PubMed  CAS  Google Scholar 

  53. Barry MK, Aloisi JD, Pickering SP, Yeo CJ. Nitric oxide modulates water and electrolyte transport in the ileum. Ann Surg. 1994; 219: 382–8.

    Article  PubMed  CAS  Google Scholar 

  54. Rao RK, Riviere PJM, Pascaud X, Junien JL, Porreca F. Tonic regulation of mouse ileal ion transport by nitric oxide. J Pharmacol Exp Ther. 1984; 269: 626–31.

    Google Scholar 

  55. Mailman D. Differential effects of lumenal L-arginine and NQnitro t.-arginine on blood flow and water fluxes in rat ileum. Br J Pharmacol. 1994; 112: 304–10.

    Article  PubMed  CAS  Google Scholar 

  56. Takeuchi K, Ohuchi T, Miyake H, Niki S, Okabe S. Effects of nitric oxide synthase inhibitors on duodenal alkaline secretion in anesthetized rats. Eur J Pharmacol. 1993; 231: 135–9.

    Article  PubMed  CAS  Google Scholar 

  57. Konturek SJ, Bilski J, Konturek PK, Cieszkowski M, Pawlik W. Role of endogenous nitric oxide in the control of canine pancreatic secretion and blood flow. Gastroenterology. 1993; 104: 896–902.

    PubMed  CAS  Google Scholar 

  58. Teppermari BL, Brown JF, Whittle BJR. Nitric oxide synthase induction and intestinal epithelial cell viability in rats. Am J Physiol. 1993; 93: G214–18.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Pharmacy, University of Wisconsin, 425 N. Charter Street, Madison, WI, 53705, USA

    T. S. Gaginella

Authors
  1. T. S. Gaginella
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. School of Pharmacy, University of Wisconsin, Madison, WI, USA

    Timothy S. Gaginella

  2. First Department of Medicine, University Medical School of Pécs, Pécs, Hungary

    Gyula Mózsik

  3. Department of Biomedical Sciences, Sheffield Hallam University, Sheffield, UK

    K. D. Rainsford

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Gaginella, T.S. (1997). Biological Oxidants as Intestinal Secretagogues. In: Gaginella, T.S., Mózsik, G., Rainsford, K.D. (eds) Biochemical Pharmacology as an Approach to Gastrointestinal Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5390-4_25

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-5390-4_25

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6267-1

  • Online ISBN: 978-94-011-5390-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation