Luminal hypotonicity increases duodenal mucosal permeability by a mechanism involving 5-hydroxytryptamine
2006 (English)In: Acta Physiologica, ISSN 1748-1708, Vol. 186, no 1, 45-58 p.Article in journal (Refereed) Published
Aim: To investigate whether 5-HT participates in the mediation of the hypotonicity-induced increase in duodenal mucosal permeability.
Methods: Proximal duodenum in anesthetized rats was perfused in situ with a hypotonic NaCl solution and effects on duodenal motility, net fluid flux, mucosal permeability (blood-to-lumen clearance of 51Cr-EDTA) and the release of 5-HT into the luminal solution studied in the presence of the cyclooxygenase inhibitor indomethacin.
Results: Perfusion of the duodenum with 50 mM NaCl increased mucosal permeability eightfold, increased the luminal output of 5-HT twofold and induced net fluid absorption. This rise in permeability was enhanced 25% by 5-HT (3 · 10-3 M), reduced by the 5-HT3-receptor antagonists granisetron (10-4 - 3 · 10-4 M) or ondansetron (10-5 - 10-4 M) or by the 5-HT4 receptor antagonist SB 203186 (10-4 M). The 5-HT3/4 receptor antagonist tropisetron, at 10-4 M, did not affect while 3 · 10-4 and 3 · 10-3 M augmented the hypotonicity-induced increase in mucosal permeability. Lidocaine (1.1 · 10-3 M) similarly potentiated while tetrodotoxin (5 · 10-5 M) inhibited the hypotonicity-induced increase in mucosal permeability. Compared to animals treated with indomethacin alone ondansetron and granisetron augmented (by 30-40%) while tropisetron and lidocaine reduced (by 60-70%) the hypotonicity-induced net fluid absorption. TTX and all 5-HT receptor antagonists, except tropisetron, depressed duodenal motility.
Conclusions: Luminal hypotonicity increases duodenal mucosal permeability by a neural mechanism involving 5-HT acting on 5-HT3 and 5-HT4 receptors. 5-HT also appears to participate in the regulation of the hypotonicity-induced fluid flux.
Place, publisher, year, edition, pages
2006. Vol. 186, no 1, 45-58 p.
Anesthetics; Local/pharmacology, Animals, Cyclooxygenase Inhibitors/pharmacology, Duodenum/drug effects/*physiology, Granisetron/pharmacology, Indoles/pharmacology, Indomethacin/pharmacology, Intestinal Mucosa/drug effects/*physiology, Lidocaine/pharmacology, Male, Ondansetron/pharmacology, Osmotic Pressure, Piperidines/pharmacology, Rats, Rats; Inbred Strains, Receptors; Serotonin; 5-HT3/antagonists & inhibitors, Receptors; Serotonin; 5-HT4/antagonists & inhibitors, Serotonin/*metabolism, Serotonin Agents/metabolism, Serotonin Antagonists/pharmacology, Tetrodotoxin/pharmacology
IdentifiersURN: urn:nbn:se:uu:diva-95372DOI: 10.1111/j.1748-1716.2005.01507.xPubMedID: 16497179OAI: oai:DiVA.org:uu-95372DiVA: diva2:169555