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Stress‐induced barrier disruption of rat follicle‐associated epithelium involves corticotropin‐releasing hormone, acetylcholine, substance P, and mast cells
Author(s) -
Keita å. v.,
Söderholm J. D.,
Ericson A.c.
Publication year - 2010
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2010.01471.x
Subject(s) - endocrinology , medicine , paracellular transport , carbachol , corticotropin releasing hormone , chemistry , substance p , receptor , acetylcholine , receptor antagonist , mast cell , biology , antagonist , hormone , permeability (electromagnetism) , neuropeptide , immunology , biochemistry , membrane
Background The follicle‐associated epithelium (FAE) is specialized in uptake and sampling of luminal antigens and bacteria. We previously showed that stress increased FAE permeability in rats. An increased uptake may alter antigen exposure in Peyer’s patches leading to intestinal disease. The aim of this study was to elucidate mechanisms involved in the acute stress‐induced increase in FAE permeability. Methods Rats were pretreated i.p. with corticotropin‐releasing hormone receptor (CRH‐R) antagonist, neurokinin receptor 1 (NK‐1R) antagonist, atropine, the mast cell stabilizer doxantrazole (DOX), or NaCl, and submitted to 1‐h acute water avoidance stress. FAE tissues were mounted in Ussing chambers for measurements of permeability to 51 Cr‐EDTA , horseradish peroxidase (HRP) and chemically killed Escherichia coli K‐12. Further, FAE segments were exposed in vitro in chambers to CRH, substance P (SP), carbachol, and DOX. Neurotransmitter‐ and receptor distribution was studied by immunohistochemistry. Key Results Stress‐induced increases in uptake across FAE of HRP and E. coli were reduced by DOX, CRH‐R antagonist and atropine, whereas the NK‐1R antagonist decreased 51 Cr‐EDTA permeability. Exposure to CRH and carbachol increased HRP and E. coli passage, whereas SP increased bacterial and 51 Cr‐EDTA permeability. DOX counteracted all of these effects. Immunohistochemistry revealed CRH, acetylcholine, SP, and their receptors on mast cells within the Peyer’s patches, subepithelial dome, and adjacent villi. Conclusions & Inferences Corticotropin‐releasing hormone and acetylcholine signaling affect mainly transcellular permeability while SP seems more selective toward the paracellular pathways. Our findings may be of importance for the understanding of the pathogenesis of stress‐related intestinal disorders.