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 hypersecretion in the small intestine. The aim of this study was to determine the effect of the 5-hydroxytryptamine receptor antagonists ketanserin, granisetron, ondansetron and tropisetron on cholera toxin-induced hypersecretion in the pig jejunum. Hypersecretion was induced by cholera toxin in ligated jejunal loops. The antagonists were administered subcutaneously at a dose of 100 micrograms/kg. Furthermore, the effect of intraluminally instilled ondansetron was studied. None of the antagonists altered basal absorption or caused fluid hypersecretion. Cholera toxin caused a dose-dependent electrolyte and fluid hypersecretion. The apparent maximal effect, 6.8 +/- 0.4 mg fluid x mg dry loop-1, was reduced by ondansetron, granisetron and tropisetron by about 40%, 30%, and 20%, respectively, whereas ketanserin had no effect. Intraluminal ondansetron reduced the effect of cholera toxin by about 50%. These results demonstrate that 5-hydroxytryptamine3 antagonists administered subcutaneously reduce the cholera toxin-induced hypersecretion in the pig jejunum. Finally, the results support species differences with respect to the antagonistic effect of the tested drugs in cholera toxin-induced hypersecretion.
Grondahi
M L
ML
Department of Anatomy and Physiology, Royal Veterinary and Agricultural University, Frederiksberg, Denmark.
Jensen
G M
GM
Skadhauge
E
E
Hansen
M B
MB
D000704:Analysis of Variance; D000818:Animals; D002772:Cholera Toxin / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D017829:Granisetron / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007579:Jejunal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000662:veterinary*; D007583:Jejunum / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology*; D017294:Ondansetron / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013552:Swine; D013553:Swine Diseases / Q000139:chemically induced* / Q000378:metabolism*; D000077526:Tropisetron
D002772:Cholera Toxin; D017829:Granisetron; D007211:Indoles; D007650:Ketanserin; D017294:Ondansetron; D012702:Serotonin Antagonists; D000077526:Tropisetron