ROLE OF 5-HYDROXYTRYPTAMINE TYPE-3 RECEPTORS IN RAT INTESTINAL FLUID AND ELECTROLYTE SECRETION INDUCED BY CHOLERA AND ESCHERICHIA-COLI ENTEROTOXINS

Cholera toxin and Escherichia coli heat labile toxin (LT) induced intestinal secretion has in the past been attributed exclusively to an increase in intracellular cAMP whereas E coli heat stable toxin (ST) induced secretion is mediated through cGMP. Evidence is accumulating on the importance of 5-hydroxytryptamine (5-HT) in cholera toxin induced secretion, but its role in LT and ST is not well established. This study therefore investigated in vivo the effect of 5-HT3 receptor antagonist, granisetron, on intestinal fluid and electrolyte secretion induced by cholera toxin, LT, and ST. Granisetron (30, 75, 150, or 300 mu g/kg) was given subcutaneously to adult male Wistar rats 90 minutes before instillation of 75 mu g cholera toxin or 50 mu g LT in isolated whole small intestine. In situ small intestinal perfusion was performed with an iso-osmotic plasma electrolyte solution (PES) to assess fluid movement. In a second group of animals, granisetron (300 mu g/kg) was given subcutaneously and two hours later small intestinal perfusion with PES containing 200 mu g/l ST was performed. Cholera toxin induced net fluid secretion (median -50.1 mu l/min/g (interquartile range -59.5 to -29.8)) was found to be dose dependently decreased or abolished by granisetron (plateau effect at 75 mu g/kg: 18 (-7.8 to 28), p<0.01). Granisetron in high dose (300 mu g/kg) however, failed to prevent LT or ST induced secretion (-52 (-121 to -71) upsilon -31 (-44 to -18), and (-39 (-49 to 17) upsilon (-22 (-39 to -3)), respectively). Sodium and chloride movement paralleled that of fluid. In conclusion, these data show that 5-HT and 5-HT3 receptors play an important part in cholera toxin induced secretion but are not involved in E coli heat stable or heat labile toxin induced secretion