KETANSERIN AND GRANISETRON REDUCE CHOLERA TOXIN-INDUCED HYPERSECRETION IN PIG JEJUNUM

Background: Serotonin antagonists have been proven antisecretory in ch olera toxin (CT)-induced hypersecretion in the small intestine of rode nts. The pig small intestine is a good model for the human small intes tine with regard to physiologic and pharmacologic processes. Methods: The antisecretory effect of intraluminally administered methysergide, renzapride, ketanserin, granisetron, and tropisetron on CT-induced hyp ersecretion was rested in isolated pig jejunal loops in vivo. Results: Methysergide, ketanserin, and granisetron reduced the hypersecretory effect of CT maximally by 25%, 80%, and 50%, respectively. Tropisetron enhanced whereas renzapride did not alter the CT response. Combinatio n of ketanserin and granisetron gave a maximal inhibitory effect of ab out 85%. Surprisingly, renzapride, granisetron, and tropisetron each i nduced hypersecretion. Taking into account the hypersecretory effect o f the antagonists, they all reduced this CT-elicited hypersecretion. C onclusions: Results suggest involvement of the 5-hydroxytryptamine-2 a nd 5-hydroxytryptamine-3 receptor subtypes as mediators in CT-induced hypersecretion in pig jejunum, and antidiarrheal therapeutic potential s of ketanserin and granisetron.