Luminal hypotonicity increases duodenal mucosal permeability by a mechanism involving 5‐hydroxytryptamine

Abstract

To investigate whether 5-hydroxytryptamine (5-HT) participates in the mediation of the hypotonicity-induced increase in duodenal mucosal permeability. 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 (51)Cr-ethylenediaminetetraacetic acid (EDTA)] and the release of 5-HT into the luminal solution studied in the presence of the cyclooxygenase inhibitor indomethacin. 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-HT(3)-receptor antagonists granisetron (10(-4)-3 x 10(-4) m) or ondansetron (10(-5)-10(-4) m) or by the 5-HT(4) receptor antagonist SB 203186 (10(-4) m). The 5-HT(3/4) 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. Luminal hypotonicity increases duodenal mucosal permeability by a neural mechanism involving 5-HT acting on 5-HT(3) and 5-HT(4) receptors. 5-HT also appears to participate in the regulation of the hypotonicity-induced fluid flux.