Uptake of organic anions by the liver has kinetic characteristics of carrier-mediated transport. The nature of the carrier and the relationship of transmembrane transport to specific cellular events such as plasma membrane binding, cellular proliferation and cytoskeletal interactions are unknown. In previous work, we studied the interaction of organic anions with purified rat liver cell plasma membrane (LPM), and identified and purified an organic anion binding protein (OABP) from a sinusoidal enriched LPM subfraction. We also defined transient selective reduction in organic anion influx in regenerating liver, liver from rats treated with nafenopin and liver from fasted rats. Influx, as quantitated by the methods we employ is independent of hepatic mass, represents specific interaction of ligand with LPM and is not influenced by intracellular events, such as protein binding or metabolism. The long-range goal is to understand the mechanism of transmembrane organic anion movement on normal liver and in various acquired and inheritable disorders.
The specific aims are: (1) To quantitate immunologically OABP in liver the function of OABP in hepatic organic anion transport. (3) To compare bilirubin and BSP binding to LPM from normal, partially hepatectomized, fasted or nafenopin-treated rats. (4) To determine whether bilirubin and BSP enter the hepatocyte by a single mechanism or by overlapping, but partially independent mechanisms. (5) To study the role of microtubules and microfilaments in transmembrane movement of organic anions in normal and regenerating liver.
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