Effects of Tropisetron, a 5-Hydroxytryptamine Type 3 Receptor Blocker, on Intestinal Secretion Induced by Cholera Toxin or Deoxycholic Acid in Rabbits In Vivo

Abstract

It has been suggested that 5-hydroxytryptamine is involved in the pathogenesis 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 fluid secretion induced respectively by cholera toxin and deoxycholic acid was investigated in rabbits using isolated loops of intestine in vivo. Marked fluid accumulation in both the jejunal and colonic loops was observed after exposure to cholera toxin and deoxycholic acid respectively. Elevation of jejunal and colonic mucosal cyclic adenosine monophosphate 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 tropisetron was observed against colonic secretion induced by deoxycholic acid. Tropisetron did not affect elevated mucosal cyclic adenosine monophosphate concentrations. The inhibitory effect of tropisetron on intestinal secretion induced by cholera toxin, which was independent of cyclic adenosine monophosphate formation, suggests that 5- hydroxytryptamine plays an important role in this type of secretion.