5-HT2 and 5-HT3 receptor subtypes mediate cholera toxin-induced intestinal fluid secretion in the rat

Gastroenterology. 1990 Jul;99(1):83-9. doi: 10.1016/0016-5085(90)91233-v.

Abstract

The mechanisms of diarrhea in Asiatic cholera have been studied extensively. Cyclic adenosine monophosphate, 5-hydroxytryptamine (5-HT), prostaglandins, and the function of neuronal structures have been implicated in the pathogenesis of cholera. To elucidate the action of 5-HT in mediating cholera secretion, in vivo experiments were performed in the rat jejunum. The inhibitory effects of the 5-HT2 receptor antagonist ketanserin and the 5-HT3 receptor antagonist ICS 205-930 were studied in cholera toxin- and 5-HT-induced fluid secretion. Both ketanserin and ICS 205-930 dose-dependently but only partially reduced the secretory effect of cholera toxin. The combination of the two blockers totally abolished cholera toxin-induced secretion without any influence on cholera toxin-induced increase in cyclic adenosine monophosphate. Prostaglandin E2- and bisacodyl-induced secretion was not affected by the combined administration of 5-HT2 and 5-HT3 antagonists. The present results provide evidence for an important role of 5-HT in cholera toxin-induced secretion. The data suggest a model in which cholera toxin may initiate the release of 5-HT from enterochromaffin cells. 5-Hydroxytryptamine may then cause prostaglandin E2 formation via 5-HT2 receptors and activation of neuronal structures via 5-HT3 receptors. These two effects may finally lead to the profuse fluid secretion which can be totally blocked by the combination of a 5-HT2 blocker and a 5-HT3 blocker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bisacodyl / pharmacology
  • Cholera Toxin / pharmacology*
  • Dinoprostone / pharmacology
  • Female
  • Indoles / pharmacology
  • Intestinal Secretions / metabolism*
  • Jejunum / drug effects
  • Jejunum / metabolism*
  • Ketanserin / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / metabolism*
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology
  • Tropisetron

Substances

  • Indoles
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Bisacodyl
  • Serotonin
  • Tropisetron
  • Cholera Toxin
  • Ketanserin
  • Dinoprostone