EFFECT OF 5-HYDROXYTRYPTAMINE ANTAGONISTS ON CHOLERA TOXIN-INDUCED SECRETION IN THE HUMAN JEJUNUM

In rats, the combined administration of the 5-HT2 antagonist ketanserin and the 5-HT3 antagonist tropisetron inhibits cholera toxin-induced intestinal secretion. We investigated whether these agents and the 5-HT3 antagonist ondansetron can inhibit cholera toxin-induced secretion in the human jejunum using a segmental perfusion technique. In a first control period the subjects' jejunums were perfused continuously with a plasma-like electrolyte solution. In a second control period they either received a combination of tropisetron plus ketanserin, or tropisetron or ondansetron alone. Cholera toxin 6.25 mu g was then administered intrajejunally and the experiments were continued for 4 h. Net water movements during the 4th hour after CT administration minus net water movement during the first control period was used for further calculation and was referred to as net luminal gain. In perfusion studies with tropisetron plus ketanserin resp. ondansetron the net luminal gain of water (+161 +/- 26 resp. 189 +/- 28 ml 30 cm(-1) h(-1), mean +/- SEM) was significantly higher compared to perfusion studies with cholera toxin alone (+94 +/- 30). Treatment with tropisetron did not change the CT-induced net luminal gain of water (+108 +/- 41). Movements of sodium, chloride, bicarbonate and potassium paralleled the movement of water. In agreement with these observations we found a deterioration of clinical parameters after the end of the perfusion studies in four of five subjects treated with CT 25 mu g plus ketanserin and tropisetron. Contrary to what has been observed in animal experiments the results in humans indicate enhancement rather than inhibition of CT-induced secretion by administration of 5-HT antagonists. Our results do not support the contention that the intravenous administration of ketanserin, tropisetron or ondansetron might be of potential therapeutic value in patients with Asiatic cholera.