We examined the effect of stress on colonic epithelial physiology, the role of corticotropin-releasing hormone (CRH), and the pathways involved. Rats were restrained or injected intraperitoneally with CRH or saline. Colonic segments were mounted in Ussing chambers, in which ion secretion and permeability (conductance and probe fluxes) were measured. To test the pathways involved in CRH-induced changes, rats were pretreated with hexamethonium, atropine, bretylium, doxantrazole, α-helical CRH-(9—41) (all intraperitoneally), or aminoglutethimide (subcutaneously). Restraint stress increased colonic ion secretion and permeability to ions, the bacterial peptide FMLP, and horseradish peroxidase (HRP). These changes were prevented by α-helical CRH-(9—41) and mimicked by CRH (50 μg/kg). CRH-induced changes in ion secretion were abolished by α-helical CRH-(9—41), hexamethonium, atropine, or doxantrazole. CRH-stimulated conductance was significantly inhibited by α-helical CRH-(9—41), hexamethonium, bretylium, or doxantrazole. CRH-induced enhancement of HRP flux was significantly reduced by all drugs but aminoglutethimide. Peripheral CRH reproduced stress-induced colonic epithelial pathophysiology via cholinergic and adrenergic nerves and mast cells. Modulation of stress responses may be relevant to the management of colonic disorders.

We have previously reported that acute stress alters intestinal transport physiology in Wistar-Kyoto rats, a stress-susceptible strain. In this study, we tested the hypothesis that the abnormalities in these rats are due to cholinergic mechanisms. Atropine- or saline-treated rats were exposed to acute restraint stress, and, subsequently, electrophysiological parameters of excised jejunal segments were assessed in Ussing chambers. Compared with the parent Wistar rat strain, Wistar-Kyoto rats demonstrated significantly greater stress-induced changes in ion secretion and permeability. The activity of cholinesterase in intestinal mucosal homogenates was significantly less in Wistar-Kyoto than in Wistar rats. Atropine pretreatment of rats before stress corrected the epithelial pathophysiology. Our results suggest that stress stimulated the release of acetylcholine, resulting in altered epithelial function in these genetically predisposed rats.

Stress may be a contributing factor in intestinal inflammatory disease; however, the underlying mechanisms have not been elucidated. We previously reported that acute stress altered jejunal epithelial physiology. In this study, we examined both physical and psychological stress-induced functional changes in colonic mucosa. Colonic mucosal tissue from rats subjected to either 2 hr of cold-restraint stress or 1 hr of water-avoidance stress demonstrated altered ionic transport as well as significantly elevated baseline conductance (ionic permeability) and flux of horseradish peroxidase (macromolecular permeability). Intraperitoneal pretreatment with the corticotropin-releasing hormone (CRH) antagonist, a helical CRH(9-41), inhibited the stress-induced abnormalities, while exogenous intraperitoneal administration of CRH, to control rats, mimicked the stress responses and in vitro CRH increased the macromolecular permeability. These results suggest that peripheral CRH mediates stress-induced colonic pathophysiology. We speculate that a stress-induced barrier defect may allow uptake of immunogenic substances into the colonic mucosa, initiating or exacerbating intestinal inflammation.