Cited by 116Gastrointestinal motility and disordersMast cells and histamineNeuropeptides and Animal Physiology

Chronic peripheral administration of corticotropin-releasing factor causes colonic barrier dysfunction similar to psychological stress

Teitelbaum, Aaron A., Gareau, Mélanie G., Jury, Jennifer, Yang, Ping Chang, Perdue, Mary H.·2008·American Journal of Physiology-Gastrointestinal and Liver Physiology

Abstract

Chronic psychological stress causes intestinal barrier dysfunction and impairs host defense mechanisms mediated by corticotrophin-releasing factor (CRF) and mast cells; however, the exact pathways involved are unclear. Here we investigated the effect of chronic CRF administration on colonic permeability and ion transport functions in rats and the role of mast cells in maintaining the abnormalities. CRF was delivered over 12 days via osmotic minipumps implanted subcutaneously in wild-type (+/+) and mast cell-deficient (Ws/Ws) rats. Colonic segments were excised for ex vivo functional studies in Ussing chambers [short-circuit current (Isc), conductance (G), and macromolecular permeability (horseradish peroxidase flux)], and analysis of morphological changes (mast cell numbers and bacterial host-interactions) was determined by light and electron microscopy. Chronic CRF treatment resulted in colonic mucosal dysfunction with increased Isc, G, and horseradish peroxidase flux in+/+but not in Ws/Ws rats. Furthermore, CRF administration caused mast cell hyperplasia and abnormal bacterial attachment and/or penetration into the mucosa only in+/+rats. Finally, selective CRF agonist/antagonist studies revealed that stimulation of CRF-R1 and CRF-R2 receptors induced the elevated secretory state and permeability dysfunction, respectively. Chronic CRF causes colonic barrier dysfunction in rats, which is mediated, at least in part, via mast cells. This information may be useful in designing novel treatment strategies for stress-related gastrointestinal disorders.

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Crossref · 10.1152/ajpgi.90210.2008

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Authors
Teitelbaum, A. A., Gareau, M. G., Jury, J., Yang, P. C., & Perdue, M. H.
Affiliations
  • McMaster University (CA)
  • University of Toronto (CA)
Venue
American Journal of Physiology-Gastrointestinal and Liver Physiology
Published
2008-09
Volume
295
Issue
3
Pages
G452-G459
ISSN
  • 0193-1857 (ISSN-L)
  • 1522-1547
OpenAlex
W2122927576
Cited by
116
References
52
Citations by year
2026: 2 · 2025: 6 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 3 · 2017: 11 · 2016: 6 · 2015: 6 · 2014: 9 · 2013: 10 · 2012: 8
FWCI
5.57
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
corticotropin-releasing factor, psychological stress, mast cells, colonic permeability, ion transport, CRF1 receptor, CRF receptor 2, short-circuit current
MeSH terms
CRF Receptor, Type 1, Animals, Bacterial Adhesion, Colon, Colonic Diseases, Corticotropin-Releasing Hormone, Disease Models, Animal, Drug Administration Schedule, Electric Conductivity, Hyperplasia, Intestinal Mucosa, Intestinal Secretions, Male, Mast Cells, Permeability, Rats, Inbred Strains, Stress, Psychological, Time Factors, Infusion Pumps, Implantable, Ion Transport, Receptors, Corticotropin-Releasing Hormone, Rats

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