Mechanisms of Hepatocyte Organic Anion Transport

The major pathways that the liver utilizes to take up and excrete various organic anions are mediated by several facilitative uptake transporters and ATP-dependent excretory pumps. Functions of the uptake transporters have been clarified in part by study of ligand processing in people with genetic polymorphisms as well as in animal models. Elucidation of excretory mechanisms for bile acids and nonbile acid organic anions was facilitated by study of inheritable disorders of bile acid and bilirubin glucuronide excretion using the tools of molecular genetics. In cholestasis, basolateral (sinusoidal) plasma membrane expression of several members of the mrp family (e.g., mrp3) is substantially increased, permitting potentially toxic bile acids and organic anions to be pumped out of the cell and back into the circulation. Future investigation into structure-function relationships and factors required for cell surface expression and activity of these transporters will be essential for ultimately understanding their function in health and disease.