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.
Evidence suggests that stress may be a contributing factor in intestinal inflammatory disease; however, the involved mechanisms have not been elucidated. We previously reported that acute stress alters epithelial physiology of rat intestine. In this study, we documented stress-induced macromolecular transport across intestinal epithelium. After exposure of Wistar-Kyoto rats to acute restraint stress, transport of a model protein, horseradish peroxidase (HRP), was assessed in isolated segments of jejunum. The flux of intact HRP was significantly enhanced across intestine from stressed rats compared with controls. Electron microscopy revealed HRP-containing endosomes within enterocytes, goblet cells, and Paneth cells of stressed rats. The number and area of HRP endosomes within enterocytes were found to be significantly increased by stress. HRP was also visualized in paracellular spaces between adjacent epithelial cells only in intestine from stressed rats. Atropine treatment of rats prevented the stress-induced abnormalities of protein transport. Our results suggest that stress, via a mechanism that involves release of acetylcholine, causes epithelial dysfunction that includes enhanced uptake of macromolecular protein antigens. We speculate that immune reactions to such foreign proteins may initiate or exacerbate inflammation.
Differential in vivo and in vitro intestinal permeability to lactulose and mannitol in animals and humans: a hypothesis Bijlsma, P.B.; Peeters, R.A.; Groot, J.A.; Dekker, P.R.; van den Meer, R.; Taminiau, J.A.J.M. Published in: Gastroenterology DOI:10.1016/0016-5085(95) Link to publication Citation for published version (APA): Bijlsma, P. B., Peeters, R. A., Groot, J. A., Dekker, P. R., van den Meer, R., & Taminiau, J. A. J. M. (1995). Differential in vivo and in vitro intestinal permeability to lactulose and mannitol in animals and humans: a hypothesis. Gastroenterology, 108, 687-696. https://doi.org/10.1016/0016-5085(95)90440-9 General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Background/Aims: Clinical interpretation of urinary recovery ratios of lactulose and mannitol is hampered by incomplete understanding of the mechanisms of transmucosal passage. The aim of this study was to compare in vivo and in vitro probe permeability. Methods: Stripped sheets of small intestine from rodents and human biopsy specimens were mounted in Ussing chambers, and mucosa-to-serosa fluxes of lactulose and mannitol were determined. Urinary recovery of orally applied probes was measured in rodents, cats, and humans. Results: In vitro lactulose/mannitol flux ratios were close to 0.8 in all species. Urinary recovery ratios differed between rodents and cats or humans; low ratios in cats and humans were due to high mannitol recovery. Conclusions: Interspecies variation in urinary recovery of mannitol is caused by differences specific for the intact small intestines in vivo. Because hyperosmolality of villus tips in vivo varies, being highest in humans and cats as a result of vascular countercurrent multiplication, it is hypothesized that the high urinary recovery of mannitol in these species is caused by solvent drag through pores that allow the passage of mannitol but not of lactulose. Therefore, the lactulose/ mannitol ratio is primarily a standard for the normal functioning of villus epithelial cells in metabolite absorption and for normal villus blood flow.T he urinary recovery ratio of orally ingested lactulose and mannitol is frequently used as a noninvasive tool in the diagnosis of intestinal disorders. An increased ratio is usually considered to be indicative of changes in small...
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