Pancreatic secretory response to intraileal amino acids - Studies in dogs with an in situ neurally isolated ileum

Background: Intraileal carbohydrates and lipids affect the pancreatic exocr ine secretion, but the effect of intraileal al-nino acids and the role of t he extrinsic nerves of the ileum as mediators of the pancreatic bicarbonate and enzyme output are unknown. Methods: Four dogs underwent total extrinsic denervation of the entire ileu m. Thomas-like cannulas were placed into the stomach, duodenum (to collect pure pancreatic juice), and at the jejuno-ileal junction. Eight neurally in tact control dogs received only the three fistulas. After recovery, in both sets of dogs, dose-response studies of the pancreatic secretory response t o intraileal infusion with graded loads of tryptophan (0. 12-10.0 mmol/h) w ere performed, given against an intravenous (iv) background of secretin (20 .5 pmol/kg/h) and cerulein (29.6 pmol/kg/h). On separate days, control expe riments with intraileal infusion of 0.15 M NaCl were performed. Results: In both sets of dogs, iv secretin plus cerulein significantly (p < 0.05) increased pancreatic bicarbonate and protein output above basal. Int raileal tryptophan caused a dose-dependent decrease in the pancreatic bicar bonate and protein response to secretin plus cerulein. In the dogs with den ervated ileum, this inhibition was significantly stronger than in the intac t animals. In both sets of dogs, the 225-min integrated bicarbonate (IBR) a nd protein response (IPR) to all loads of tryptophan were significantly low er than in control experiments. Both IBR and IPR were significantly lower i n the denervated as compared with the intact animals. Conclusions: 1) Extrinsic denervation of the entire ileum is a valuable pre paration to study the role of nerves in the control of pancreatic exocrine secretion; 2) both in the intact and denervated animals the amino acid tryp tophan induces an "ileal brake" of the hormonally stimulated pancreatic bic arbonate and protein output; 3) the extrinsic nerves of the ileum are proba bly not the dominant mediators of the inhibitory action of intraileal trypt ophan but rather counteract this effect.