Potentiating effect of bile on enterotoxin-induced diarrhea

The influence of bile acids on adenosine 3',5'-phosphate-induced intestinal secretion was studied in mice. Bile flow was stopped by ligation of the common bile duct, and secretion was induced in ligated loops of the small intestine. The decrease of bile led to inhibition of hypersecretion after challenge with heat-labile enterotoxins from Vibrio cholerae and Escherichia coli, as well as with prostaglandin E1. In contrast, the fluid response induced by dibutyryl-adenosine 3',5'-phosphate was unaffected by intestinal bile. Injection of bile or bile acids into intestinal loops before cholera toxin challenge restored the toxin-induced secretion in the bile-depleted intestine. At the subcellular level the decrease of intestinal bile led to inhibition of cholera toxin-activated adenylate cyclase, whereas the bile concentration did not influence the binding of 125I-labeled toxin to the intestinal epithelial cells. The results suggest that intestinal bile interacts with adenylate cyclase in the induction of fluid secretion by enterotoxins and prostaglandin E1.