The aim of this research is to determine what, if any, is the role of the Golgi apparatus in bile acid secretion in the liver. We have found that purified Golgi from rat liver, as well as plasma membranes and cytoplasm, contain high affinity binding sites for taurocholate. We will characterize further what proteins are involved in this binding and determine what relationship, if any, exists between binding proteins of Golgi, plasma membranes and the cytoplasm. The ability of the various subcellular organelles of liver to take up bile salts will be investigated using filtration techniques. We have developed such techniques for studying nucleotide transport in Golgi vesicles. If uptake is found in isolated Golgi and/or other subcellular organelles, we will characterize the uptake with respect to its kinetic parameters and determine how its properties relate to the high and low affinity binding sites observed in these fractions. Finally, using rat liver cell suspensions, we will perturb albumin secretion at the level of the Golgi apparatus and determine the effects on bile salt secretion. These studies will help define the subcellular pathway of bile acid secretion in liver and thus have a direct bearing on medical problems such as cholestasis, gallstones and their treatment, cirrhosis, and liver diseases in general. The metabolism and secretion of bile acids also affects cholesterol metabolism in the liver and thus this research is also relevant to atherosclerosis.
