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.

Project Start
1983-04-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Kaiser, J; Stockert, R J; Wolkoff, A W (1988) Effect of monensin on receptor recycling during continuous endocytosis of asialoorosomucoid. Exp Cell Res 174:472-80
Wolkoff, A W; Samuelson, A C; Johansen, K L et al. (1987) Influence of Cl- on organic anion transport in short-term cultured rat hepatocytes and isolated perfused rat liver. J Clin Invest 79:1259-68
Stockert, R J; Grushoff, P S; Morell, A G et al. (1986) Transport and intracellular distribution of copper in a human hepatoblastoma cell line, HepG2. Hepatology 6:60-4
Paietta, E; Stockert, R J; Morell, A G et al. (1986) Lectin activity as a marker for Hodgkin disease cells. Proc Natl Acad Sci U S A 83:3451-5
Kaiser, J; Stockert, R J; Schein, P S et al. (1986) Recognition of hepatitis B surface antigen by the human hepatoma cell line HepG2. Trans Assoc Am Physicians 99:86-91
Wolkoff, A W; Stockert, R J (1986) Selective expression of hepatocellular membrane proteins in mice homozygous for a lethal chromosomal deletion. Proc Soc Exp Biol Med 181:270-4
Paietta, E; Stockert, R J; Morell, A G et al. (1986) Unique antigen of cultured Hodgkin's cells. A putative sialyltransferase. J Clin Invest 78:349-54
Wolkoff, A W; Sosiak, A; Greenblatt, H C et al. (1985) Immunological studies of an organic anion-binding protein isolated from rat liver cell plasma membrane. J Clin Invest 76:454-9
Goresky, C A; Bach, G G; Wolkoff, A W et al. (1985) Sequestered tracer outflow recovery in multiple indicator dilution experiments. Hepatology 5:805-14
Stollman, Y R; Theilmann, L; Stockert, R J et al. (1985) Reduced transport of bilirubin and asialoorosomucoid in regenerating rat liver is a microtubule-independent event. Hepatology 5:798-804