M B Hansen1, E Skadhauge. 1. Dept. of Anatomy and Physiology, Royal Veterinary and Agricultural University, Frederiksberg, Denmark.
Abstract
BACKGROUND: Serotonin antagonists have been proven antisecretory in cholera toxin (CT)-induced hypersecretion in the small intestine of rodents. The pig small intestine is a good model for the human small intestine with regard to physiologic and pharmacologic processes. METHODS: The antisecretory effect of intraluminally administered methysergide, renzapride, ketanserin, granisetron, and tropisetron on CT-induced hypersecretion was tested 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. Combination of ketanserin and granisetron gave a maximal inhibitory effect of about 85%. Surprisingly, renzapride, granisetron, and tropisetron each induced hypersecretion. Taking into account the hypersecretory effect of the antagonists, they all reduced this CT-elicited hypersecretion. CONCLUSIONS: Results suggest involvement of the 5-hydroxytryptamine-2 and 5-hydroxytryptamine-3 receptor subtypes as mediators in CT-induced hypersecretion in pig jejunum, and antidiarrheal therapeutic potentials of ketanserin and granisetron.
BACKGROUND:Serotonin antagonists have been proven antisecretory in cholera toxin (CT)-induced hypersecretion in the small intestine of rodents. The pig small intestine is a good model for the human small intestine with regard to physiologic and pharmacologic processes. METHODS: The antisecretory effect of intraluminally administered methysergide, renzapride, ketanserin, granisetron, and tropisetron on CT-induced hypersecretion was tested 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. Combination of ketanserin and granisetron gave a maximal inhibitory effect of about 85%. Surprisingly, renzapride, granisetron, and tropisetron each induced hypersecretion. Taking into account the hypersecretory effect of the antagonists, they all reduced this CT-elicited hypersecretion. CONCLUSIONS: Results suggest involvement of the 5-hydroxytryptamine-2 and 5-hydroxytryptamine-3 receptor subtypes as mediators in CT-induced hypersecretion in pig jejunum, and antidiarrheal therapeutic potentials of ketanserin and granisetron.