Acetorphan prevents cholera-toxin-induced water and electrolyte secretion in the human jejunum.
OBJECTIVE
Acetorphan is an orally administered inhibitor of enkephalinase in the wall of the digestive tract. It prevents inactivation of endogenous opioid peptides released by submucosal and myenteric neurons. The aim of this study was to examine the effect of acetorphan on jejunal water and electrolyte transport in healthy volunteers under basal conditions and in a state of intestinal secretion induced by a bacterial enterotoxin.


METHODS
Ten volunteers in two groups were studied in an open trial. For the experimental design an intestinal perfusion technique was used.


METHODS
Cholera toxin was used to induce intestinal secretion in a model employing segmental perfusion of the human proximal jejunum. Acetorphan was given orally prior to intrajejunal administration of cholera toxin; its effect on intestinal transport was measured over a period of four hours after exposure to cholera toxin. Serum levels of methylthioether of thiorphan as the main metabolite were measured throughout three experiments to assure sufficient drug absorption.


RESULTS
Acetorphan had no influence on basal water and electrolyte absorption (133 vs. 140 ml/30 cm x h). In a control group with cholera toxin alone, significant water secretion was induced (131 ml/30 cm x h). Acetorphan completely prevented this secretion by leaving an absorption rate of 27 ml/30 cm x h. Intestinal electrolyte transport was also significantly changed towards absorption by acetorphan.


CONCLUSIONS
Acetorphan can prevent jejunal water and electrolyte secretion induced by cholera toxin. Enkephalins may thus protect the small intestine from enterotoxin-induced secretion.
Hinterleitner
T A
TA
Department of Internal Medicine, Karl Franzens University, Graz, Austria.
Petritsch
W
W
Dimsity
G
G
Berard
H
H
Lecomte
J M
JM
Krejs
G J
GJ
D000328:Adult; D002772:Cholera Toxin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004573:Electrolytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology; D015244:Thiorphan / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D014867:Water / Q000378:metabolism*
D004573:Electrolytes; D011480:Protease Inhibitors; D014867:Water; C049331:racecadotril; D002772:Cholera Toxin; D015244:Thiorphan