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.
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References
Gaginella TS, Kachur JF, Tamai H, Keshavarzian A. Reactive oxygen and nitrogen metabolites as mediators of secretory diarrhea. Gastroenterology. 1995; 109: 2019–28.
Caprilli R, Sopranzi N, Colaneri O. Salt losing diarrhea in idiopathic proctocolitis. Scand J Gastroenterol. 1978; 13: 331–5.
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.
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.
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.
Head LH, Heaton JW Jr, Kivel RM. Absorption of water and electrolytes in Crohn’s disease of the colon. Gastroenterology. 1969; 56: 571–9.
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.
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.
Bjarnasson I, O’Morain C, Levi AJ, Peters AJ. Absorption of 51chromium-labeled ethylenediaminetetraacetate in inflammatory bowel disease. Gastroenterology. 1983; 85: 318–22.
Rachmilewitz D, Karmeli F, Sharon P. Decreased colonic Na-K-ATPase activity in active ulcerative colitis. Israel 7 Med Sci. 1984; 20: 681–4.
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.
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.
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.
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.
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.
Rachmilewitz D, Stamler JSJ, Karmeli F et al. Peroxynitrite-induced rat colitis–a new model of colonic inflammation. Gastroenterology. 1993; 105: 1681–8.
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.
Halliwell B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet. 1994; 344: 721–4.
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.
Gaginella TS. Receptor pharmacology of intestinal secretion. In: Lebenthal E, Duffey M, eds. Secretory Diarrhea. New York, NY: Raven Press; 1990: 163–78.
Gaginella TS, Kachur JF. Kinins as mediators of intestinal secretion. Am J Physiol. 1989; 256: G1 - G15.
Gaginella TS. Eicosanoid-mediated intestinal secretion. In: Lebenthal E, Duffey M, eds. Secretory Diarrhea. New York, NY: Raven Press; 1990: 15–30.
Gaginella TS. Absorption and secretion in the colon. Curr Opin Gastroenterol. 1995; 11: 2–8.
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.
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.
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.
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.
Donowitz M. Arachidonic acid metabolites and their role in inflammatory bowel disease: An update requiring addition of a pathway. Gastroenterology. 1985; 85: 50–587.
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.
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.
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.
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.
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.
MacNaughton WK. Nitric oxide-donating compounds stimulate electrolyte transport in the guinea pig intestine in vitro. Life Sci. 1993; 53: 585–93.
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.
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.
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.
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.
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.
Izzo A, Gaginella TS, Mascolo N, Cappasso F. Nitric oxide as a mediator of the laxative action of magnesium sulphate. 1994; 113: 228–32.
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.
Schmidt HHHW. NO, CO and OH endogenous soluble guanylate cyclase-activating factors. Fed Eur Biochem Soc. 1992; 307: 102–7.
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.
DeJonge HR. The localization of guanylate cyclases in rat small intestinal epithelium. FEBS Lett. 1975; 53: 237–42.
Craven PA, DeRubertis FR. Cyclic nucleotide metabolism in rat colonic epithelial cells with different proliferative activities. Biochem Biophys Acta. 1981; 676: 155–69.
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.
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.
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.
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.
Brasitus TA, Field M, Kimberg DV. Intestinal mucosal cyclic GMP: regulation and relation to ion transport. Am J Physiol. 1976; 231: G275–82.
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.
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.
Barry MK, Aloisi JD, Pickering SP, Yeo CJ. Nitric oxide modulates water and electrolyte transport in the ileum. Ann Surg. 1994; 219: 382–8.
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.
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.
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.
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.
Teppermari BL, Brown JF, Whittle BJR. Nitric oxide synthase induction and intestinal epithelial cell viability in rats. Am J Physiol. 1993; 93: G214–18.
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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
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DOI: https://doi.org/10.1007/978-94-011-5390-4_25
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