Abstract
Stress may be a contributing factor in intestinal inflammatory disease; however, the underlying mechanisms have not been elucidated. We previously reported that acute stress altered jejunal epithelial physiology. In this study, we examined both physical and psychological stress-induced functional changes in colonic mucosa. Colonic mucosal tissue from rats subjected to either 2 hr of cold-restraint stress or 1 hr of water-avoidance stress demonstrated altered ionic transport as well as significantly elevated baseline conductance (ionic permeability) and flux of horseradish peroxidase (macromolecular permeability). Intraperitoneal pretreatment with the corticotropin-releasing hormone (CRH) antagonist, α helical CRH9–41, inhibited the stress-induced abnormalities, while exogenous intraperitoneal administration of CRH, to control rats, mimicked the stress responses and in vitro CRH increased the macromolecular permeability. These results suggest that peripheral CRH mediates stress-induced colonic pathophysiology. We speculate that a stress-induced barrier defect may allow uptake of immunogenic substances into the colonic mucosa, initiating or exacerbating intestinal inflammation.
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REFERENCES
Sullivan A: Psychogenic factors in ulcerative colitis. Am J Dig Dis 2:651–656, 1935
Duffy LC, Zielezny MA, Marshall JR, Byers TE, Weiser MM, Phillips JF, Calkins BM, Ogra PL, Graham S: Relevance of major stress events as an indicator of disease activity prevalence in inflammatory bowel disease. Behav Med 17:101–110, 1991
Talal AH, Drossman DA: Psychosocial factors in inflammatory bowel disease. Gastroenterol Clin North Am 24:699–716, 1995
Levenstein S, Prantera C, Varvo V, Scribano ML, Berto E, Andreoli A, Luzi C: Psychological stress and disease activity in ulcerative colitis: a multidimensional cross-sectional study. Am J Gastroenterol 89:1219–1225, 1994
Greene BR, Blanchard EB, Wan CK: Long-term monitoring of psychosocial stress and symptomatology in inflammatory bowel disease. Behav Res Ther 32:217–226, 1994
Fava GA, Pavan L: Large bowel disorders. I. Illness configuration and life events. Psychother Psychosomat 27:93–99, 1976
Fiocchi C: Inflammatory bowel disease: Etiology and pathogenesis. Gastroenterol 115:182–205, 1998
Wyatt J, Vogelsang H, Hübl W, Waldhör T, Lochs H: Intestinal permeability and the prediction of relapse in Crohn's disease. Lancet 341:1437–1439, 1993
Glavin GB: Restraint ulcer: History, current research and future implications. Brain Res Bull 5:51–58, 1980
Bueno L, Collins SM, Junien JL: Stress and Digestive Motility. London, John Libby Publishers, 1989
Monnikes H, Schmidt BG, Raybould HE, Taché Y: CRH in the paraventricular nucleus mediates gastric and colonic motor response to restraint stress. Am J Physiol 262:G137–G143, 1992
Empey LR, Fedorak RN: Effect of misoprostol in preventing stress-induced intestinal fluid secretion in rats. Prostaglandins Leukotrienes Essent Fatty Acids 38:43–48, 1989
Castagliuolo I, LaMont JT, Qiu B, Fleming SM, Bhaskar KR, Nikulasson ST, Kornetsky C, Pothoulakis C: Acute stress causes mucin release from rat colon: Role of corticotropin releasing factor and mast cells. Am J Physiol 271:G884–G892, 1996
Andrianopoulos G, Bombeck CT, Nyhus LM: Influence of maturation on activity-stress related pathology in the rat colon. Physiol Behav 36:1105–1110, 1986
Saunders PR, Kosecka U, McKay DM, Perdue MH: Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine. Am J Physiol 267:G794–G799, 1994
Pare WP: Stress ulcer susceptibility and depression in Wistar Kyoto (WKY) rats. Physiol Behav 46:993–998, 1989
Saunders PR, Hanssen NPM, Perdue MH: Cholinergic nerves mediate stress-induced intestinal transport abnormalities in Wistar Kyoto rats. Am J Physiol 237:G486–G490, 1997
Kiliaan AJ, Saunders PR, Bijlsma PB, Berin MC, Taminiau JA, Groot JA, Perdue MH: Stress stimulates transepithelial macromolecular uptake in rat jejunum. Am J Physiol (in press)
Berin MC, Kiliaan AJ, Yang PC, Groot JA Taminiau JAJM, Perdue MH: Rapid transepithelial antigen transport in rat jejunum: impact of sensitization and the hypersensitivity reaction. Gastroenterology 113:856–864, 1997
Bijlsma PB, Kiliaan AJ, Scholten G, Heyman M, Groot JA, Taminiau JAJM: Carbachol but not forskolin can increase mucosal to serosal transport of intact protein in rat ileum in vitro. Am J Physiol 271:G147–G155, 1996
Blair EH, Wing RR, Wald A: The effect of laboratory stressors on glycemic control and gastrointestinal transit time. Psychosom Med 53:133–143, 1991
Yoshimura H, Kan N, Ogawa N: Preventive and curative effects of prostaglandins on stress ulcer in rats (application of endoscopic observation). Dig Dis Sci 34:436–444, 1989
Barclay GR, Turnberg LA: Effect of psychological stress on salt and water transport in the human jejunum. Gastroenterology 93:91–97, 1987
Barclay GR, Turnberg LA: Effect of cold-induced pain on salt and water transport in the human jejunum. Gastroenterology 94:994–998, 1988
Barclay GR, Turnberg LA: Effect of moderate exercise on salt and water transport in the human jejunum. Gut 29:816–820, 1988
Rubio CA, Sveander M, Duvander A: A model to evaluate acute and chronic stress in the colonic mucosa of rats. Dis Colon Rectum 32:26–29, 1989
Morrow NS, Garrick T: Effects of intermittent tail shock or water avoidance on proximal colonic motor contractility in rats. Physiol Behav 62:233–239, 1997
Santos J, Saunders PR, Hanssen NPM, Yang P-C, Yates D, Groot JA, Perdue MH: Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat. Am J Physiol 277:G391–G399, 1999
Overton JM, Fisher LA: Differentiated hemodynamic responses to central versus peripheral administration of corticotropin-releasing factor in conscious rats. J Autonom Nerv Syst 35:43–52, 1991
Schäfer M, Mousa SA, Stein C: Corticotropin-releasing factor in antonociception and inflammation. Eur J Pharmacol 323:1–10, 1997
Karalis K, Sano H, Redwine J, Listwak S, Wilder RL, Chrousos GP: Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo. Science 254:421–423, 1991
Kawahito Y, Sano H, Mukai S, Asai K, Kimura S, Yamamura YY, Kato H, Chrousos GP, Wilder RL, Kondo M: Corticotropin releasing hormone in colonic mucosa in patients with ulcerative colitis. Gut 37:544–551, 1995
van Tol EAF, Petrusz P, Lund PK, Yamauchi M, Sartor RB: Local production of corticotropin releasing hormone is increased in experimental intestinal inflammation in rats. Gut 39:385–392, 1996
Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty T, Rotter JI: Increased intestinal permeability in patients with Crohn's disease and their relatives. Ann Intern Med 105:883–885, 1986
May GR, Sutherland LR, Meddings JB. Is small intestinal permeability really increased in relatives of patients with Crohn's disease? Gastroenterology 104:1627–1632, 1993
Qiu BS, Vallance BA, Blennerhassett PA, Collins SM: The role of CD4+ lymphocytes in the susceptibility of mice to stressinduced reactivation of experimental colitis. Nature Med 5:1178–1182, 1999
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Saunders, P.R., Santos, J., Hanssen, N.P. et al. Physical and Psychological Stress in Rats Enhances Colonic Epithelial Permeability via Peripheral CRH. Dig Dis Sci 47, 208–215 (2002). https://doi.org/10.1023/A:1013204612762
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DOI: https://doi.org/10.1023/A:1013204612762
- colonic mucosa
- epithelium
- permeability
- stress
- corticotropin-releasing hormone