HEPATIC UPTAKE AND TRANSPORT MECHANISMS

Although specific liver cell plasma membrane (LPM) receptor proteins have been implicated in ligand uptake by the liver, the determinants of their function and the influence of other LPM constituents such as carbohydrates and lipids are unclear. Previous studies of LPM receptor function have been performed in systems in which receptors have been purified, removing them from their normal milieu, or in isolated membranes or cells in which normal cellular architecture has been destroyed. The isolated perfused rat liver enables these studies to be performed in a viable, intact organ free of hemodynamic and hormonal alterations which may complicate interpretation of studies performed in intact animals. The specific aims of the proposed research are: (1) to study the effect of specific modifications to the LPM surface on transport of organic anions and asialoglycoproteins, (2) to study the role of specific cytoskeletal elements (microtubules, microfilaments, and calmodulin) on hepatic transport of asialoglycoproteins and organic anions, (3) to study the possible role of the asialoglycoprotein receptor in hepatic uptake and biliary excretion of polymeric IgA and (4) to define normal uptake kinetics of other ligands which may have receptor-mediated uptake mechanisms. These ligands will include copper, lipoproteins, protoporphyrins and bilirubin photoisomers.