Abstract

The effect of plasma sampled in 2 children with WDS related to ganglioneuroblastoma was tested on the cultured cell line HT 29, derived from adenocarcinoma of human colon, that was found to possess a highly sensitive (3 × 10−12 M) cAMP system specific for VIP. Results showed that: 1) plasma from children with WDS strongly stimulated cAMP accumulation in HT 29 cells, whereas plasma from normal children did not elicit any significant rise; 2) stimulation induced by serial diluticnsof plasma from children with WDS paralleled the dose-effect of standard VIP; 3) there was no more stimulating effect when plasma was previously exposed to specific anti-VIP antibody; 4) plasma sampled after arrest of diarrhea, either spontaneous or following surgical resection of the tumor, was ineffective; 5) stimulation elicited by acid extracts of tumors and by standard VIP were identical. Further assessment of the biological significance of these data was provided by epithelial cells isolated from normal human colon. In these cells, cAMP accumulation was also stimulated by plasma from children with WDS. It can be concluded that the systems studied provide useful models for measurement of the biological effect of plasma from children with WDS on human intestinal epithelium. It appears that, at least in some cases, WDS is related to circulating VIP.

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