EFFECTS OF TROPISETRON, A 5-HYDROXYTRYPTAMINE TYPE-3 RECEPTOR BLOCKER, ON INTESTINAL SECRETION INDUCED BY CHOLERA-TOXIN OR DEOXYCHOLIC-ACIDIN RABBITS IN-VIVO

It has been suggested that 5-hydroxytryptamine is involved in the path ogenesis of various intestinal hypersecretory states including cholera . In this study, the effect of tropisetron (ICS 205-930), a specific 5 -hydroxytryptamine type-3 receptor blocker, on jejunal and colonic flu id secretion induced respectively by cholera toxin and deoxycholic aci d was investigated in rabbits using isolated loops of intestine in viv o. Marked fluid accumulation in both the jejunal and colonic loops was observed after exposure to cholera toxin and deoxycholic acid respect ively. Elevation of jejunal and colonic mucosal cyclic adenosine monop hosphate concentrations was also noted. Intraperitoneal administration of tropisetron dose-dependent inhibited jejunal secretion induced by cholera toxin. In contrast, no significant anti-secretory effect of tr opisetron was observed against colonic secretion induced by deoxycholi c acid. Tropisetron did not affect elevated mucosal cyclic adenosine m onophosphate concentrations. The inhibitory effect of tropisetron on i ntestinal secretion induced by cholera toxin, which was independent of cyclic adenosine monophosphate formation, suggests that 5-hydroxytryp tamine plays an important role in this type of secretion.