Polyspecific organic cation transporters and their biomedical relevance in kidney

Secretion and reabsorption of organic cations in kidney is mediated by polyspecific transporters with broadly overlapping substrate specificity. Knowledge concerning function, transported compounds, clinical impact of mutations in the transporters and drug-drug interactions is rapidly increasing. Recent research concerning properties of these transporters and their clinical significance for nephrology is summarized.

Recent data showed that the organic cation transporters OCT1-3 form homo-oligomers, and that oligomerization is important for transporter targeting to the plasma membrane. A functional relevant substrate binding hinge domain in these transporters has been identified. Screening of 900 prescription drugs for interaction with the H-organic cation transporter hMATE1 indicated that 10% of the drugs are inhibitors and that 0.5% are effective under clinical conditions. The pivotal role of hOCT2 for renal secretion of creatinine and metformin was confirmed in clinical studies.

Organic cation transporters of the transporter families SLC22 and SLC47 are critically involved in the renal secretion of various cationic drugs. Drug-drug interactions at the transporter level and mutations in the transporters lead to changes in pharmacokinetics and influence nephrotoxicity of drugs. Further studies are required to improve drug therapies.