After drinking water, the fluid quickly leaves the stomach thereby creating a hypotonic luminal environment in the duodenum. This in turn constitutes a potential threat to the integrity of the duodenal epithelium. It therefore seems highly likely that luminal hypotonicity activates physiological mechanisms that aim to increase luminal osmolality. One such physiological mechanism may be to increase mucosal permeability thereby facilitating the transport of osmolytes into the lumen. A draw-back of performing experiments in anesthetized animals is that surgery per se depresses gut functions, such as peristalsis, by mechanisms involving endogenous prostaglandins. In this thesis it is shown that inhibition of cyclooxygenase-2 (COX-2), in animals subjected to an abdominal operation, restore and/or improve duodenal functions such as motility, mucosal bicarbonate secretion, hypotonicity-induced increase in mucosal permeability and the osmolality-adjusting capability. Experiments revealed that the stomach is resistant to hypotonic challenge while the jejunum is more sensitive to hypotonicity-induced increase in mucosal permeability than the duodenum. The hypotonicity-induced increase in duodenal mucosal permeability is not due to injury but possibly reflects physiological dilatation of paracellular shunts. Luminal perfusion of the duodenum with an isotonic solution lacking Cl- decreased bicarbonate secretion while the lack of luminal Na+ increased mucosal permeability. Stimulation of bicarbonate secretion by COX-2 inhibition is to a large extent dependent on luminal Cl- while that induced by vasoactive intestinal peptide is not. The hypotonicity-induced increase in mucosal permeability involves the release and action of serotonin (5-HT) on 5-HT3 and 5-HT4 receptors and stimulation of enteric nerves strongly implicating physiological regulation of this process.
| Identifer | oai:union.ndltd.org:UPSALLA1/oai:DiVA.org:uu-7444 |
| Date | January 2007 |
| Creators | Pihl, Liselotte |
| Publisher | Uppsala universitet, Institutionen för neurovetenskap, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, info:eu-repo/semantics/doctoralThesis, text |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 217 |
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