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The impact of cyclooxygenase inhibition on duodenal motility and mucosal alkaline secretion in anaesthetized rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
2011 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 201, no 1, 179-192 p.Article, review/survey (Refereed) Published
Abstract [en]

Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of various human diseases. However, these drugs also have serious adverse effects in the gastrointestinal tract. In the duodenum NSAIDs inhibit mucosal alkaline secretion (DMAS), an important protective mechanism against the acid emptied from the stomach in most species, including humans. Surprisingly, NSAIDs have been shown to stimulate DMAS in an anaesthetized rat model. The aim of this review was to summarize the effects of NSAIDs and selective cyclooxygenase-2 (COX-2) inhibition on duodenal function in the rat and provide an explanation for why these drugs stimulate DMAS. Included are new data examining the effect of alpha-adrenergic drugs on duodenal motility and DMAS. Methods: Experiments were performed in anaesthetized rats. The proximal duodenum was perfused luminally with an isotonic NaCl solution. DMAS, motility, fluid flux and epithelial permeability were assessed in the absence and presence of various COX inhibitors. Results: COX inhibition induced duodenal motility, increased DMAS and augmented the sensitivity as well as the maximal response of the duodenal mucosa to lidocaine- or hypotonicity-induced increases in mucosal permeability. Furthermore, the ability of the duodenum to absorb water and to adjust osmolality in response to luminal hypotonicity was improved in COX-inhibited animals. These improvements are mediated predominately via inhibition of COX-2. Conclusions: Inhibition of COX-2 in rats with postoperative duodenal ileus induces muscle contractions, which in turn activate a nicotinic receptor-dependent intramural reflex that stimulates duodenocytes to increase the activity of apical Cl-/HCO3- exchangers, resulting in a rise in DMAS.

Place, publisher, year, edition, pages
2011. Vol. 201, no 1, 179-192 p.
Keyword [en]
bicarbonate secretion, fluid flux, indomethacin, mucosal permeability, parecoxib, postoperative ileus
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-142838DOI: 10.1111/j.1748-1716.2010.02196.xISI: 000285153100019PubMedID: 20887356OAI: oai:DiVA.org:uu-142838DiVA: diva2:388300
Available from: 2011-01-17 Created: 2011-01-17 Last updated: 2011-01-17Bibliographically approved

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