부산대학교 도서관

Aim: To investigate whether 5-hydroxytryptamine (5-HT) participates in the mediation 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 51Cr-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 × 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 (TTX) (5 × 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. [ABSTRACT FROM AUTHOR]