Analysis of amino acid residues in the predicted transmembrane pore influencing transport kinetics of the hepatic drug transporter organic anion transporting polypeptide 1B1 (OATP1B1)

摘要

The hepatic uptake transporters OATPIB1 (SLCO1B1) and OATP1B3 (SLC61B3) mediate the uptake of endogenous metabolites and drugs from blood into hepatocytes. Alterations of transport function are accompanied with variations in drug plasma concentrations and the risk of adverse drug effects. Thus, knowledge on amino acids determining substrate recognition or transport kinetics are important to predict alterations in transport kinetics. Therefore, we analyzed the charged amino acids His54 and Tyr169, both located at the extracellular entry of the predicted transmembrane pore of OATP1B1.