Jejunal cAMP-activated sodium secretion via deconjugated bile salts and fatty acids

Abstract

Jejunal cAMP-activated sodium secretion associated with in vivo intraluminal bile salts and free fatty acid accumulation in the small bowel was studied. Wistar rats (70–90 g) were treated with mecamylamine HCl (20 mg/kg twice daily, × 3 days); this ganglionic blocking agent allows bacterial overgrowth of the small bowel with colonic anaerobes. Controls were given 0.9% NaCl. Half of each group was fed 4% cholestyramine resin in a commercial lab chow; the other half received the same diet without this resin. The contents of the small intestine were assayed for free fatty acids, bile salts, and enterotoxin activity. Jejunal sodium and 3- O-methyl- d-glucose transport rates were assessed by in vivo perfusions. Jejunal mucosa was studied for ATPases and cAMP. Mecamylamine-treated rats had significantly higher jejunal luminal concentrations of free fatty acids and bile salts. Deconjugated bile salts were notably elevated, principally cholate. There was no enterotoxic activity detectable. Mecamylamine treatment was also associated with jejunal sodium secretion and a three-fold increase in mucosal cAMP concentrations, while control rats absorbed sodium and had no alterations in cAMP levels. Dietary cholestyramine treatment ameliorated the intestinal derangements induced by mecamylamine. Resin-treated rats had reduced luminal free fatty acids and deconjugated bile salts, while sodium was absorbed in the jejunum and mucosal cAMP levels were comparable to controls. Mecamylamine treatment did not alter (Na +-K +)-ATPase activity or jejunal transport of 3- O-methyl- d-glucose at a 4 m m concentration. These data indicate that during small bowel overgrowth with colonic bacteria following mecamylamine treatment in rats, there is a cAMP-mediated sodium secretion associated with increased luminal free fatty acids and deconjugated bile salts.