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Products of cyclooxygenase-2 depress duodenal function in rats subjected to abdominal surgery
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
2006 (English)In: Acta Physiologica, ISSN 1748-1708, Vol. 186, no 4, 279-90 p.Article in journal (Refereed) Published
Abstract [en]

Aim: Abdominal surgery evokes powerful biological responses that affect gastrointestinal functions. Here we investigate the role of the COX-1 and COX-2 isoforms in postoperative duodenal ileus.

Methods: Proximal duodenum of anesthetized rats was perfused in situ with isotonic or hypotonic (50 mM) NaCl. Mucosal bicarbonate secretion, motility, mucosal permeability and effluent osmolality were determined in the absence and presence of different COX inhibitors.

Results: The majority of control animals had no or few duodenal contractions and bicarbonate secretion averaged 10.9 ± 1.4 µmol · cm-1 · h-1. These “paralytic” controls responded to hypotonic NaCl with a small increase in mucosal permeability. In control animals exhibiting spontaneous duodenal contractions the bicarbonate secretion was 50% higher and the hypotonicity-induced net increase in mucosal permeability 7-fold higher than in “paralytic” controls. Treatment with the selective COX-2 inhibitors rofecoxib or parecoxib induced duodenal motility, increased bicarbonate secretion and potentiated the hypotonicity-induced increase in mucosal permeability. COX-2-inhibited animals had a twofold greater capacity to adjust luminal osmolality than “paralytic” controls. The selective COX-1 inhibitor SC-560 only transiently stimulated motility and bicarbonate secretion and the hypotonicity-induced increase in mucosal permeability was smaller than in COX-2 inhibited animals.

Conclusions: Abdominal surgery increases the synthesis of prostanoids, particularly via the COX-2 isoform. This compromises the ability of the duodenum to contract and to secrete HCO3- and to adjust luminal osmolality possibly via altered mucosal permeability. It is proposed that studies of gastrointestinal functions in animals subjected to abdominal surgery should include animals pre-treated with a COX-2 inhibitor.

Place, publisher, year, edition, pages
2006. Vol. 186, no 4, 279-90 p.
Keyword [en]
Animals, Bicarbonates/metabolism, Cyclooxygenase 1/metabolism, Cyclooxygenase 2/*metabolism, Cyclooxygenase Inhibitors/pharmacology, Duodenum/*metabolism, Gastrointestinal Motility/drug effects, Intestinal Absorption/drug effects, Intestinal Mucosa/drug effects/*metabolism, Isoxazoles/pharmacology, Lactones/pharmacology, Laparotomy/*adverse effects, Male, Osmolar Concentration, Perfusion, Pyrazoles/pharmacology, Rats, Rats; Inbred Lew, Sodium Chloride/pharmacology, Sulfones/pharmacology
National Category
URN: urn:nbn:se:uu:diva-95369DOI: 10.1111/j.1748-1716.2006.01559.xPubMedID: 16634783OAI: oai:DiVA.org:uu-95369DiVA: diva2:169552
Available from: 2007-01-12 Created: 2007-01-12 Last updated: 2009-10-16Bibliographically approved
In thesis
1. Luminal Hypotonicity and Duodenal Functions: An Experimental Study in the Rat
Open this publication in new window or tab >>Luminal Hypotonicity and Duodenal Functions: An Experimental Study in the Rat
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 59 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 217
Physiology, luminal alkalinization, mucosal permeability, osmolality, cyclooxygenase-2, rat, duodenum, jejunum, motility, enteric nervous system, Fysiologi
urn:nbn:se:uu:diva-7444 (URN)978-91-554-6778-4 (ISBN)
Public defence
2007-02-02, B21, BMC, Norra vägen, Uppsala, 09:15
Available from: 2007-01-12 Created: 2007-01-12Bibliographically approved

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