Crucial role for 5-HT in cholera toxin but not Escherichia coli heat-labile enterotoxin-intestinal secretion in rats

Gastroenterology. 1998 Oct;115(4):883-90. doi: 10.1016/s0016-5085(98)70260-4.


Background & aims: Many consider cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) to be functionally identical. Both increase intracellular adenosine 3',5'-cyclic monophosphate concentration; however, differences between the two and the severity of the diseases they cause have been reported. The secretagogue 5-hydroxytryptamine (5-HT) is implicated in CT-induced secretion, but its role in LT-induced secretion is unclear. We tested the hypothesis that LT fails to recruit 5-HT in its secretory processes.

Methods: In vivo small intestinal perfusions were undertaken in adult male Wistar rats after incubation with equipotent doses of CT or LT, or saline. Small intestinal 5-HT release and the effect on net small intestinal water and electrolyte transport of (1) pharmacological depletion of 5-HT; (2) blockade of 5-HT type 2, 3, and 4 receptors; and (3) pretreatment with lidocaine, hexamethonium, and atropine were determined.

Results: CT- but not LT-induced secretion was accompanied by 5-HT release, reduced by 5-HT depletion, and inhibited by each 5-HT antagonist. By contrast, lidocaine and hexamethonium inhibited secretion induced by both toxins.

Conclusions: LT induces secretion without recruiting a 5-HT-dependent cascade. This may account for differences in clinical severity of the diseases CT and LT cause and has implications for the development of antisecretory therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Toxins / pharmacology*
  • Cholera Toxin / pharmacology*
  • Enterotoxins / pharmacology*
  • Escherichia coli Proteins*
  • Fenclonine / pharmacology
  • Intestine, Small / drug effects*
  • Intestine, Small / metabolism*
  • Male
  • Neural Inhibition / physiology
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology
  • Tissue Distribution


  • Bacterial Toxins
  • Enterotoxins
  • Escherichia coli Proteins
  • Serotonin Antagonists
  • Serotonin
  • Cholera Toxin
  • heat-labile enterotoxin, E coli
  • Fenclonine