Corticotropin‐releasing factor 1 receptor‐mediated mechanisms inhibit colonic hypersensitivity in rats

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Abstract
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.