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- Title
Corticotropin-releasing factor 1 receptor-mediated mechanisms inhibit colonic hypersensitivity in rats.
- Authors
Greenwood-Van Meerveld, B.; Johnson, A. C.; Cochrane, S.; Schulkin, J.; Myers, D. A.
- Abstract
The potential relationship between stress and irritable bowel syndrome (IBS) symptomatology suggests a possible role for stress-mediating hormones, such as corticotropin-releasing factor (CRF), in the altered perception of stimuli in IBS patients. In previous studies, Wistar–Kyoto (WKY) rats with genetic indices of high anxiety demonstrated colonic hypersensitivity coupled with a high basal level of CRF within the central nervous system. In the current study we tested the hypothesis that a selective, non-peptide CRF1 receptor antagonist, antalarmin, would inhibit hypersensitivity in the WKY rat colon. Colonic sensitivity was determined by monitoring a visceromotor behavioural response during innocuous levels of colorectal distention (30 mmHg). In high anxiety WKY rats we found that antalarmin (20 mg kg−1, i.p.) significantly decreased the visceromotor response induced by colorectal distention. In a second study central administration (i.c.v.) of CRF was used to induce colonic hypersensitivity in lower anxiety Fischer 344 (F-344) rats, and in this model, antalarmin significantly inhibited the CRF-induced colonic hypersensitivity. In summary, a selective CRF1 receptor antagonist, antalarmin, inhibits colonic hypersensitivity apparent in WKY rats or in F-344 rats given a central administration of CRF. Our findings suggest that CRF1 receptor antagonism may represent a novel therapeutic approach for the treatment of IBS.
- Subjects
CORTICOTROPIN releasing hormone; IRRITABLE colon; NEUROPEPTIDES; COLON diseases; RATS
- Publication
Neurogastroenterology & Motility, 2005, Vol 17, Issue 3, p415
- ISSN
1350-1925
- Publication type
Article
- DOI
10.1111/j.1365-2982.2005.00648.x