Cyclic AMP accumulation in human colon adenocarcinoma cells in culture (HT-29) is known to be particularly sensitive to the stimulating action of vasoactive intestinal peptide (VIP). This property was exploited as a means of investigating the possible role of VIP as a humoral mediator in the watery diarrhoea syndrome. Our results showed that plasma from two patients with watery diarrhoea syndrome associated with ganglioneuroblastoma and pheochromocytoma strongly stimulated cyclic AMP accumulation in HT-29 cells, whereas plasma from normal subjects and patients with other diarrhoeal disorders had no effect. The stimulation induced by serial dilutions of plasma from patients paralleled the VIP-induced response. Preincubation of these plasmas with specific anti-VIP antibody prevented their stimulatory effects. Plasma sampled after the arrest of diarrhoea (spontaneous or after surgical resection of tumours) elicited AMP rise in HT-29 cells. Tumour extract stimulated cyclic AMP accumulation in HT-29 cells with a dose-response curve which was superimposable on the one obtained with standard VIP. The results lend support to the hypothesis that VIP is a humoral mediator in WDS and suggest that the diarrhoea is mediated through a VIP-induced accumulation of cyclic AMP in intestinal epithelial cells.
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