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

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 51 Cr‐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 m m 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‐HT 3 ‐receptor antagonists granisetron (10 −4 –3 × 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 × 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‐HT 3 and 5‐HT 4 receptors. 5‐HT also appears to participate in the regulation of the hypotonicity‐induced fluid flux.