Figure[s10] 1.

Routes of uptake of drugs into cells of the renal proximal tubule (simplified to show only major paths). Organic anions and cations are transported across cell membranes by the proteins of the organic anion transporter (OAT) and organic cation transporter (OCT) (SLC22) family of transporters, which have differing (poly) specificities and different expression patterns on the apical and basal sides of cells, thus driving vectorial transport. These exchange import of organic anions for export of ketogluratate and similar molecules, the transmembrane gradient of which is established by other processes that are powered, ultimately, by the Na/K ATPase. The imported anions and cations exit either passively or via active exchangers such as P-glycoprotein. If no efficient exit route exists, either for the imported molecule or its metabolites, there is a risk the cytoplasmic concentrations will become toxic. Small proteins and other molecules, such as aminoglycosides, are recovered from the luminal space by endocytosis driven by the megalin – cubulin system. Some organic cations (such as choline) are also recovered from the lumen by various transport systems [35].