X Gui, RE Carraway. Department of Physiology, Univ. of Medical School, Worcester, MA 01655
We investigated the role of neurotensin (NT), an intestinal hormone released by fat ingestion, as a possible regulator of bile acid (BA) secretion and recirculation. In fasted rats whose common bile ducts were cannulated for bile collection, NT infusion at near physiologic levels (10 pmol/kg.min iv) increased bile flow and BA output during the 3 hr experiment but only in animals given donor bile into duodenum at near basal bile flow rate (30 ml/min). The fact that NT enhanced BA output only when the concentration of intestinal BA was maintained suggested that NT's effect was on the return of BA from intestine to liver (which is known to be rate-determining in the normal process). In rats prepared as above and given 3H-labeled taurocholate (3H-TC, 5mM, 1ml) into duodenum or into ileum, NT infusion (3-10 pmol/kg.min iv) increased by 2-4 fold the recovery rate of 3H-TC in bile. When cholate was substituted for taurocholate, the effect of NT was not observed. Thus, exogenous NT at near physiologic levels stimulated transport of conjugated BA from intestine to liver. In order to investigate the role of endogenous NT in lipid-stimulated BA secretion, rats were given 20% Intralipid (fat emulsion, 3 ml) intraduodenally with either 3H-TC or donor bile and the effect of NT antagonist SR48692 (500 nmol/kg.min iv) was tested. SR48692 reduced bile flow and recovery rate for 3H-TC and BA in bile. This suggested that endogenous NT participated in the regulation of lipid-stimulated BA circulation. Overall, these results are consistent with the idea that NT is an enhancer for the enterohepatic circulation of BA and that it acts primarily by promoting the transport of conjugated BA from intestine to liver.
Work supported by NIH Grant DK28565
* Presented on the Endocrine Society's 81st Annual Meeting, June 12-15, 1999, San Diego
Postdoctoral Research Position available
Start immediately. To perform endocrine studies on Nerotensin (NT), an intestinal peptide implicated in the regulation of enterohepatic systems, fat digestion and triglyceride / lipoprotein metabolism. Other work focuses on NT as a metabolic signal coordinating nutritional status with reproductive functions.
We seek a scientist with training and enthusiasm for lipid metabolism and /or reproductive endocrinology.
Abilities could include the following: bioassays with animals / tissue culture, immunoassay, receptor assays,
receptor/G protein signal transduction, lipid chemistry, molecular biology. Send CV with a comprehensive personal
statement directly to
Dr. Robert E. Carraway.