Chenodeoxycholic acid-induced diarrhea in rats: effects of atropine and codeine

Orally administered chenodeoxycholic acid (300 mg/kg) produced diarrhea and accumulation of gastro-intestinal fluid in rats. The fluid in the stomach and small intestine remained accumulated even after the accumulated colonic fluid and the diarrheal excretion decreased. When instilled into an intestinal closed-loop, chenodeoxycholic acid caused a marked inhibition of fluid absorption in the colon and jejunum but less effect in the ileum. On the contrary, an intravenous administration of chenodeoxycholic acid caused neither diarrhea nor impairment of colonic absorption of fluid. Atropine and codeine (10 mg/kg s.c.) blocked or at least delayed the diarrhea produced by oral administration of chenodeoxycholic acid. The antidiarrheal activity of codeine was found to be more potent and longer-lasting than that of atropine. Both drugs delayed the passage of chenodeoxycholic acid containing gastric fluid into the duodenum, but neither of them prevented chenodeoxycholic acid-induced jejunal secretion of fluid and electrolytes. These results indicate that the diarrheal excretion by chenodeoxycholic acid was ascribable to the impairment of fluid absorption in the colonic mucosa and partly to the activation of gastro-intestinal propulsive motility.