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.
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