Journal
ACTA PHYSIOLOGICA
Volume 186, Issue 1, Pages 45-58Publisher
WILEY
DOI: 10.1111/j.1748-1716.2005.01507.x
Keywords
enteric nervous system; fluid transport; indomethacin; motility; post-operative ileus; rat
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Aim: To investigate whether 5-hydroxytryptamine (5-HT) participates in the mechation of the hypotonicity-induced increase in duodenal mucosal permeability. Methods: Proximal duodenum in anaesthetized 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 Cr-51-ethylenediaminetetraacetic acid (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 X 10(-3) m), reduced by the 5-HT3-receptor antagonists granisetron (10(-4)-3 x 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 x 10-4 and 3 x 10-3 m augmented the hypotonicity-induced Increase in mucosal permeability. Lidocaine (1.1 X 10(-3) m) similarly potentiated while tetrodotoxin (TTX) (5 X 10(-5) M) inhibited the hypotonicity-induced increase in mucosal permeability. Compared with 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. Tetrodotoxin 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.
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