Molecular pharmacology of renal organic anion transporters

Renal organic anion transport systems play an important role in the elimina tion of drugs, toxic compounds, and their metabolites, many of which are po tentially harmful to the body. The renal proximal tubule is the primary sit e of carrier-mediated transport from blood to urine of a wide variety of an ionic substrates. Recent studies have shown that organic anion secretion in renal proximal tubule is mediated by distinct sodium-dependent and sodium- independent transport systems. Knowledge of the molecular identity of these transporters and their substrate specificity has increased considerably in the past few years by cloning of various carrier proteins. However, a numb er of fundamental questions still have to be answered to elucidate the part icipation of the cloned transporters in the overall tubular secretion of an ionic xenobiotics. This review summarizes the latest knowledge on molecular and pharmacological properties of renal organic anion transporters and hom ologs, with special reference to their nephron and plasma membrane localiza tion, transport characteristics, and substrate and inhibitor specificity. A number of the recently cloned transporters, such as the p-aminohippurate/d icarboxylate exchanger OAT1, the anion/sulfate exchanger SAT1, the peptide transporters PEPT1 and PEPT2, and the nucleoside transporters CNT1 and CNT2 , are key proteins in organic anion handling that possess the same characte ristics as has been predicted from previous physiological studies. The role of other cloned transporters, such as MRP1, MRP2, OATP1, OAT-K1, and OAT-K 2, is still poorly characterized, whereas the only information that is avai lable on the homologs OAT2, OAT3, OATP3, and MRP3-6 is that they are expres sed in the kidney, but their localization, not to mention their function, r emains to be elucidated.