5-hydroxytryptamine release into human jejunum by cholera toxin.

BACKGROUND Cholera toxin produces intestinal secretion by activation of the adenylate cyclase complex. However animal studies have shown 5-hydroxytryptamine may be released after exposure to cholera toxin, and thereby contribute to the secretory state. AIM To determine whether cholera toxin releases 5-hydroxytryptamine in human jejunum. SUBJECTS Seven male subjects were given a subclinical dose of cholera toxin in a paired, controlled, randomised, double blind study. METHODS A closed 10 cm segment of upper jejunum was exposed to 15 micrograms of cholera toxin for two hours prior to closed segment perfusion with plasma electrolyte solution containing a non-absorbable volume marker, [14C]-polyethylene glycol. 5-Hydroxytryptamine in jejunal effluent and 5-hydroxyindoleacetic acid in urine (up to seven hours after cholera toxin) were measured by high performance liquid chromatography with fluorimetric detection. RESULTS In contrast with controls, all subjects secreted fluid in response to cholera toxin, median-2.1 ml/cm/h (interquartile range-4.1 to -0.1). During seven hours following cholera toxin, 5-hydroxytryptamine was secreted into the lumen (range 31 to 395 nmol/l) but not in control experiments. After exposure to cholera toxin median urinary 5-hydroxyindoleacetic acid was 5.7 (4.1 to 6.3), which was similar to controls 4.9 (4.1 to 6.3), which was similar to controls 4.9 (4.1 to 6.2). CONCLUSION Thus, cholera toxin induced a secretory state and promoted the release of 5-hydroxytryptamine into the intestinal lumen, but quantitative changes in urinary 5-hydroxyindoleacetic acid were not detectable. As an intestinal secretagogue, these findings suggest that 5-hydroxytryptamine may play a part in mediating cholera toxin induced secretion in humans.