The goal of the proposed research is to provide new information on the complex process of bile formation. Previous work had suggested that hormon l factors have an important role in the regulation of bile formation. Specifically, the choleretics insulin and glucagon markedly inhibited the secretion of biliary cholesterol and phospholipid during bile salt stabilization. In addition, the tetradecapeptide somatostatin was found to markedly inhibit biliary secretion probably indirectly via inhibition of GI hormone release and has been a useful model for study of physiological hormonal control. Recent work identified that nerves may also be important in the regulation of hepatic biliary lipid secretion. Selective chemical sympathectomy caused a marked reduction in biliary cholesterol, phospholipi , and bile salt secretion during somatostatin inhibition of feeding choleresi . The present proposal is designed to study in more detail the possible neurohumoral factors in biliary secretion, and to apply some of the basic concepts learned to the human.
The specific aims i nclude a re-investigatio of the influence of vagotomy on biliary secretion, studies of the effects o catecholamines in some of the newer """"""""neuropeptides,"""""""" a determination of the time course of return of sympathetic function after denervation, and an establishment of the hormonal profiles in hepatectomized animals in humans as well the initial patterns of hepatobiliary secretion following liver transplantation. The proposed studies will use four animal models which ha e already been developed in our laboratory which include: (1) the chronic bi e fistula dog, (2) the in situ isolated perfused rodent liver, (3) the hepatectomized rat, and (4) rat liver transplants. Human studies on the neurohumoral control of bile formation will utilize a triple lumen t-tube a d a protocol already in use and approved by our hospital's institutional revi w board. The proposed studies potentially would increase our understanding o the basic mechanisms of bile formation, pathophysiology of gallbladder disease, fatty liver, arteriosclerosis, and liver transplantation. Increas d understanding of the neurohumoral control of biliary secretion potentially will have some impact on the clinical management of liver transplant patients, particularly in the immediate postoperative period.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035490-09
Application #
3233816
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1986-09-01
Project End
1994-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
9
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Foley, D P; Collins, B R; Magee, J C et al. (2000) Bile acids in xenogeneic ex-vivo liver perfusion: function of xenoperfused livers and compatibility with human bile salts and porcine livers. Transplantation 69:242-8
Sue, S R; Chari, R S; Kong, F M et al. (1995) Transforming growth factor-beta receptors and mannose 6-phosphate/insulin-like growth factor-II receptor expression in human hepatocellular carcinoma. Ann Surg 222:171-8
Collins, B H; Chari, R S; Magee, J C et al. (1995) Immunopathology of porcine livers perfused with blood of humans with fulminant hepatic failure. Transplant Proc 27:280-1
Saperstein, L A; Jirtle, R L; Farouk, M et al. (1994) Transforming growth factor-beta 1 and mannose 6-phosphate/insulin-like growth factor-II receptor expression during intrahepatic bile duct hyperplasia and biliary fibrosis in the rat. Hepatology 19:412-7
Chari, R S; Collins, B H; Magee, J C et al. (1994) Brief report: treatment of hepatic failure with ex vivo pig-liver perfusion followed by liver transplantation. N Engl J Med 331:234-7
Farouk, M; Vigna, S R; Haebig, J E et al. (1993) Secretin receptors in a new preparation of plasma membranes from intrahepatic biliary epithelium. J Surg Res 54:1-6
Thomson, H J; Geoghegan, J G; Farouk, M et al. (1993) Exogenous neuropeptide Y blocks myoelectric activity in the upper gastrointestinal tract of starved dogs. Brain neuropeptide Y converts a fasting pattern of myoelectric activity to a fed pattern. Scand J Gastroenterol 28:469-74
Pruthi, R S; Farouk, M; Tsai, W H et al. (1993) The effect of octreotide on hepatic regeneration in rats. Surgery 113:84-9
Farouk, M; Geoghegan, J G; Pruthi, R S et al. (1992) Intracerebroventricular neuropeptide Y stimulates bile secretion via a vagal mechanism. Gut 33:1562-5
Farouk, M; Vigna, S R; McVey, D C et al. (1992) Localization and characterization of secretin binding sites expressed by rat bile duct epithelium. Gastroenterology 102:963-8

Showing the most recent 10 out of 19 publications