Neurotensin elevates hepatic bile acid secretion in chickens by a mechanism requiring an intact enterohepatic circulation

Neurotensin (NT), given intravenously at 10-50 pmol/kg per min to anestheti zed female chickens equipped with a bile duct fistula, dose-dependently ele vated hepatic bile flow and bile acid output but only when the enterohepati c circulation was maintained by returning the bile to the intestinal lumen. Infusion of NT at 10 and 50 pmol/kg per min increased the average hepatic bile acid output over a 30-min period to 138 +/- 11 and 188 +/- 13% of cont rol, respectively. During infusion of NT, plasma levels of immunoreactive N T (iNT) increased in time from the basal level (14 +/- 1.3 pM) to reach ste ady state at 30 min. There was a near linear relationship between the dose of NT infused and the increment in plasma INT. In addition, infusion of NT at 40 pmol/kg min gave a plasma level of INT (congruent to 88 pM) which was within the range of those observed during duodenal perfusion with lipid (5 4-300 pM) and near to that measured in hepatic portal blood from fed animal s (52 +/- 5 pM). Perfusion of duodenum with lipid released endogenous NT an d increased the rate of hepatic bile flow. When NT antagonist SR48692 was g iven, bile flow rate decreased to the basal level. These results suggest th at intestinal NT, released by lipid, may participate in the regulation of h epatic bile acid output by a mechanism requiring an intact enterohepatic ci rculation. (C) 2000 Elsevier Science Inc. AU rights reserved.