INHIBITION OF 5-HYDROXYTRYPTAMINE-INDUCED AND ENTEROTOXIN-INDUCED FLUID SECRETION BY 5-HT RECEPTOR ANTAGONISTS IN THE RAT JEJUNUM

The effects of cholera toxin and heat stable Escherichia coli (E. coli ) enterotoxin on intestinal fluid secretion are commonly considered to be mediated by cyclic nucleotides. It was demonstrated recently, by u sing the 5-hydroxytryptamine (5-HT)2 receptor antagonist ketanserin an d the 5-HT3 receptor antagonist tropisetron, that 5-HT acts as an impo rtant mediator in cholera toxin- and heat stable E. coli enterotoxin-i nduced fluid-secretion. In the present investigation ketanserin and tr opisetron were compared with the newer 5-HT3 receptor antagonists onda nsetron and granisetron versus 5-HT-, cholera toxin- and heat stable E . coli enterotoxin-induced fluid secretion in the rat jejunum in vivo. Both ondansetron and granisetron dose-dependently inhibited 5-HT- and enterotoxin-induced fluid secretion. Ketanserin blocked 5-HT-induced fluid secretion, but only diminished enterotoxin-induced effects even at higher doses. Tropisetron inhibited 5-HT-and cholera toxin-induced effects at high dose but only diminished heat stable E. coli enterotox in-induced effects. We conclude that 5-HT3 receptors, located on enter ochromaffin cells and nervous structures, are more important in mediat ing fluid secretion than 5-HT2 receptors, located on the epithelial ce lls.