Crucial role for 5-HT in cholera toxin but not Escherichia coli heat-labile enterotoxin-intestinal secretion in rats.
OBJECTIVE
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.
Turvill
J L
JL
Digestive Diseases Research Centre, St. Bartholomew's and The Royal London School of Medicine and Dentistry, London, England.
Mourad
F H
FH
Farthing
M J
MJ
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D002772:Cholera Toxin / Q000494:pharmacology*; D004768:Enterotoxins / Q000494:pharmacology*; D029968:Escherichia coli Proteins; D010134:Fenclonine / Q000494:pharmacology; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009433:Neural Inhibition / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014018:Tissue Distribution
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D012702:Serotonin Antagonists; D012701:Serotonin; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli; D010134:Fenclonine