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Membrane transport and the human small intestine: Relation to mucosal protection, intestinal anaphylaxis and nitric oxide
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The tightly adherent monolayer of epithelial cells that line the luminal side of the intestine provides a dynamic and highly regulated barrier to the passive and active transport of ions, water and macromolecules. Cathecol-O-methyl transferase inhibition prevents tissue degradation of catecholaminesincluding dopamine and intracellular carbonic anhydrase activity is an important regulator of ion and water transport in the small intestine. Intestinal anaphylaxis trigger multiple effector cells and constitute adriving force for changes in active ion and water transport. Nitric oxide protect and damage the gastrointestinal mucosa through a variety of mechanisms and intestinal obstruction is caused at least in part by the activation of nerves and participation of the enteric nervous system.

Studies were made in humans with the LOCI-GUT technique with isolation of a duodenal or jejunal segment between balloons. Duodenal mucosal bicarbonate secretion increased in response to the COMT inhibitor nitecapone, similar in magnitude to that obtained by a prostaglandin E1 analogue. Acetazolamide pretreatment significantly decreased mean basal and PGE2-stimulated HCO3- secretion as well as PGE2 stimulated secretion of Cl-, Na+, K+, and water.

Challenge with different intestinal antigens induced a mucosal release of several inflammatory mediators. The parallel increase in albumin and hyaluronan illustrated the local anaphylactic reaction and is probably related to a mucosal lymphoedema. Basal net absorption of Cl- and Na+ ions and water was also changed into a net secretion.

Further studies regarding mucosal transport in the human small intestine revealed that nitric oxide is continuously synthesized and released into the intestinal lumen in a concentration of 1/100 of that in the stomach. Cephalic-vagal stimulation with sham feeding did not increase NO synthesis, but intestinal obstruction dose-dependently and significantly increased this synthesis. Inhibition of nerve stimulation by luminal lidocaine totally abolished this increase, supporting the importance of the enteric nervous system in the pathophysiology of bowel obstruction.

The data in the present thesis enlightens some of the mechanisms regulating gastrointestinal function in a specie important to ourselves.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2000. , 83 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 910
Keyword [en]
Surgery, albumin, bicarbonate secretion, carbonic anhydrase, dopamine, duodenum, histamine, humans, hyaluronan, intestinal anaphylaxis, intestinal obstruction, jejunum, lidocaine, LOC-I-GUT, nitecapone, nitric oxide, potential difference, prostaglandins, segmental intestinal perfusion
Keyword [sv]
National Category
Research subject
URN: urn:nbn:se:uu:diva-431ISBN: 91-554-4662-0OAI: oai:DiVA.org:uu-431DiVA: diva2:164820
Public defence
2000-04-07, Grönwallsalen, Akademiska sjukhuset, ingång 70, Uppsala, Uppsala, 09:15
Available from: 2000-03-17 Created: 2000-03-17Bibliographically approved

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