Corticotropin-releasing factor directly mediates colonic responses to stress

Abstract

A new stress model in rats produced changes in intestinal function that resemble patterns of intestinal dysfunction associated with stress in humans: small intestinal transit was inhibited, large intestinal transit was stimulated, and fecal excretion was stimulated. To evaluate the role of corticotropin-releasing factor (CRF) in mediating the effects of stress on the intestine, we studied the actions of exogenous CRF on small and large intestinal transit in the rat and characterized the effects of pharmacological blockade of CRF receptors on stress-induced intestinal dysfunction. Administration of exogenous CRF (0.3-10.0 micrograms iv or icv) resulted in dose-related inhibition of gastric emptying, inhibition of small intestinal transit, stimulation of colonic transit, and stimulation of fecal excretion. The actions of exogenous CRF mimicked the effects of stress on the motor activity of the gastrointestinal tract. Administration of alpha-helical CRF-(9-41) (50 micrograms iv or icv), an antagonist of CRF, prevented the stress-induced increase in large intestinal transit and the associated increase in fecal excretion. These data suggest that endogenous CRF may mediate stress-induced changes in colonic function.