Corticosterone mediates stress‐related increased intestinal permeability in a region‐specific manner

Abstract Background Chronic psychological stress (CPS) is associated with increased intestinal epithelial permeability and visceral hyperalgesia. It is unknown whether corticosterone (CORT) plays a role in mediating alterations of epithelial permeability in response to CPS. Methods Male rats were subjected to 1‐h water avoidance (WA) stress or subcutaneous CORT injection daily for 10 consecutive days in the presence or absence of corticoid receptor antagonist RU‐486. The visceromotor response (VMR) to colorectal distension (CRD) was measured. The in situ single‐pass intestinal perfusion was used to measure intestinal permeability in jejunum and colon simultaneously. Key Results We observed significant decreases in the levels of glucocorticoid receptor (GR) and tight junction proteins in the colon, but not the jejunum in stressed rats. These changes were largely reproduced by serial CORT injections in control rats and were significantly reversed by RU‐486. Stressed and CORT‐injected rats demonstrated a threefold increase in permeability for PEG‐400 (MW) in colon, but not jejunum and significant increase in VMR to CRD, which was significantly reversed by RU‐486. In addition, no differences in permeability to PEG‐4000 and PEG‐35 000 were detected between control and WA groups. Conclusions & Inferences Our findings indicate that CPS was associated with region‐specific decrease in epithelial tight junction protein levels in the colon, increased colon epithelial permeability to low molecular weight macromolecules which were largely reproduced by CORT treatment in control rats and prevented by RU‐486. These observations implicate a novel, region‐specific role for CORT as a mediator of CPS‐induced increased permeability to macromolecules across the colon epithelium.