Luminal hypotonicity increases duodenal mucosal permeability by a mechanism involving 5-hydroxytryptamine.
OBJECTIVE
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 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.


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.
Department of Neuroscience, Division of Physiology, Biomedical Center, Uppsala University, Uppsala, Sweden. olof.nylander@fysiologi.uu.se
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D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects / Q000502:physiology*; D017829:Granisetron / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D009997:Osmotic Pressure; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D018490:Serotonin Agents / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D000077526:Tropisetron
D000779:Anesthetics, Local; D016861:Cyclooxygenase Inhibitors; D017829:Granisetron; D007211:Indoles; D007213:Indomethacin; D008012:Lidocaine; D017294:Ondansetron; D010880:Piperidines; D012701:Serotonin; D058831:Serotonin 5-HT3 Receptor Antagonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D013779:Tetrodotoxin; D000077526:Tropisetron; C088817:(1-piperidinyl)ethyl 1H-indole-3-carboxylate