EFFECT OF 5-HT2 AND 5-HT3 RECEPTOR ANTAGONISTS ON CHOLERA TOXIN-INDUCED FLUID HYPERSECRETION IN THE PIG JEJUNUM

5-Hydroxytryptamine is a mediator in cholera toxin-induced hypersecret ion in the small intestine. The aim of this study was to determine the effect of the 5-hydroxytryptamine receptor antagonists ketanserin, gr anisetron, ondansetron and tropisetron on cholera toxin-induced hypers ecretion in the pig jejunum. Hypersecretion was induced by cholera tox in in ligated jejunal loops. The antagonists were administered subcuta neously at a dose of 100 mu g/kg. Furthermore, the effect of intralumi nally instilled ondansetron was studied. None of the antagonists alter ed basal absorption or caused fluid hypersecretion. Cholera toxin caus ed a dose-dependent electrolyte and fluid hypersecretion. The apparent maximal effect, 6.8 +/- 0.4 mg fluid x mg dry loop was reduced by ond ansetron, granisetron and tropisetron by about 40 %, 30 %, and 20 %, r espectively, whereas ketanserin had no effect. Intraluminal ondansetro n reduced the effect of cholera toxin by about 50 %. These results dem onstrate that 5-hydroxytryptamine(3) antagonists administered subcutan eously reduce the cholera toxin-induced hypersecretion in the pig jeju num. Finally, the results support species differences with respect to the antagonistic effect of the tested drugs in cholera toxin-induced h ypersecretion.