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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK023026-08
Application #
3227216
Study Section
(GCN)
Project Start
1979-03-01
Project End
1987-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
8
Fiscal Year
1986
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
Bejarano, Eloy; Murray, John W; Wang, Xintao et al. (2018) Defective recruitment of motor proteins to autophagic compartments contributes to autophagic failure in aging. Aging Cell :e12777
Murray, John W; Yin, David; Wolkoff, Allan W (2017) Reduction of organelle motility by removal of potassium and other solutes. PLoS One 12:e0184898
Roy-Chowdhury, Jayanta; Roy-Chowdhury, Namita; Listowsky, Irving et al. (2017) Drug- and Drug Abuse-Associated Hyperbilirubinemia: Experience With Atazanavir. Clin Pharmacol Drug Dev 6:140-146
Wang, Xintao; Wang, Pijun; Wang, Wenjun et al. (2016) The Na(+)-Taurocholate Cotransporting Polypeptide Traffics with the Epidermal Growth Factor Receptor. Traffic 17:230-44
Murray, John W; Han, Dennis; Wolkoff, Allan W (2014) Hepatocytes maintain greater fluorescent bile acid accumulation and greater sensitivity to drug-induced cell death in three-dimensional matrix culture. Physiol Rep 2:
Wang, Wen-Jun; Murray, John W; Wolkoff, Allan W (2014) Oatp1a1 requires PDZK1 to traffic to the plasma membrane by selective recruitment of microtubule-based motor proteins. Drug Metab Dispos 42:62-9
Yuan, Fei; Snapp, Erik L; Novikoff, Phyllis M et al. (2014) Human liver cell trafficking mutants: characterization and whole exome sequencing. PLoS One 9:e87043
Wolkoff, Allan W (2014) Organic anion uptake by hepatocytes. Compr Physiol 4:1715-35
Mukhopadhyay, Aparna; Quiroz, Jose A; Wolkoff, Allan W (2014) Rab1a regulates sorting of early endocytic vesicles. Am J Physiol Gastrointest Liver Physiol 306:G412-24
Choi, Jo H; Murray, John W; Wolkoff, Allan W (2011) PDZK1 binding and serine phosphorylation regulate subcellular trafficking of organic anion transport protein 1a1. Am J Physiol Gastrointest Liver Physiol 300:G384-93

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