Stress neuropeptides evoke epithelial responses via mast cell activation in the rat colon

Abstract

Previously, we showed that corticotropin-releasing factor (CRF) injected i.p. mimicked epithelial responses to stress, both stimulating ion secretion and enhancing permeability in the rat colon, and mast cells were involved. However, the ability of CRF-sensitive mucosal/submucosal loops to regulate intestinal barrier and the participation of resident mast cells are unclear. We examined colonic epithelial responses to stress-like peptides in Wistar-Kyoto (WKY), and mast cell-deficient (Ws/Ws) and their +/+ littermate control rats in distal segments mounted in Ussing chambers. Short-circuit current (ion secretion), flux of horseradish peroxidase (macromolecular permeability), and the release of rat mast cell protease II were measured in response to CRF [10(-6) to 10(-8)M] or sauvagine [10(-8) to 10(-10)M] in tissues pretreated with astressin, doxantrazole, or vehicle. Stress-like peptides (sauvagine > CRF) induced a dose-dependent increase in short-circuit current (maximal at 30 min), and significantly enhanced horseradish peroxidase flux and protease II release in WKY. Epithelial responses were inhibited by both astressin and doxantrazole, and significantly reduced in tissues from Ws/Ws rats. The stress mediators CRF and sauvagine modulate barrier function in the rat colon acting on mucosal/submucosal CRF receptor-bearing cells, through mast cell-dependent pathways.