Ketanserin and Granisetron Reduce Cholera Toxin-Induced Hypersecretion in Pig Jejunum

Abstract

Hansen MB, Skadhauge E. Ketanserin and granisetron reduce cholera toxin-induced hypersecretion in pig jejunum. Scand J Gastroenterol 1994;29:908-915.

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 antidianheal therapeutic potentials of ketanserin and granisetron.

Key Words:

• Antagonists
• cholera toxin
• intestinal secretion
• pharmacology
• physiology
• pig
• serotonin