Abstract
Stress-induced intestinal barrier dysfunction may be involved in chronic intestinal disorders. Glucagon-like peptide-2 (GLP-2) is an intestinotrophic growth hormone that can rapidly improve intestinal epithelial barrier function. Here, we investigated whether mouse intestine is responsive to chronic psychological stress and whether pretreatment with GLP-2 can ameliorate stress-induced changes. Mice were subjected to water avoidance stress (WAS; 1 h/day for 10 days) with GLP-2 or saline administered 4 h before each WAS session. After the final stress period, the intestine was removed for assessment of physiological/morphological changes. Compared with controls (sham-stressed mice), stressed mice demonstrated enhanced ion secretion and permeability in the jejunum, ileum, and colon. In addition, increased numbers of bacteria were observed adhering to and/or penetrating the epithelium, associated with infiltration of mononuclear cells into the mucosa. GLP-2 treatment improved intestinal barrier function in stressed mice and ameliorated other aspects of impaired host defense. Our study extends previous findings in rats of stress-induced intestinal dysfunction and provides insights into potential novel therapeutics.
Footnotes
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This research was supported by a grant to M.H.P. from the Crohn's and Colitis Foundation of Canada and by Astra Hässle AB. H.L.C. was the recipient of an Ontario Graduate Scholarship. H.L.C. is a Ph.D. student in the Medical Science Program at McMaster University. This work was presented at the 2003 American Gastroenterology Association Digestive Disease Week, Orlando, FL, May 17-22 (abstract #100619). Gastroenterology124 (Suppl 1):A300.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.105.085373.
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ABBREVIATIONS: IBS, irritable bowel syndrome; GLP-2, glucagon-like peptide-2; WAS, water avoidance stress; HRP, horseradish peroxidase.
- Received February 23, 2005.
- Accepted March 24, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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