The kidney: UNIQUE TRANSPORTERS EXIST FOR PEPTIDES, CONJUGATES, HYDROPHOBIC DRUGS AND NUCLEOSIDES(1)

Peptide transporters are involved in the electrogenic hydrogen-coupled cotransport of dipeptides and tripeptides. The drive for this comes from an inward hydrogen gradient and a negative transmembrane potential difference. Two homologous PEPTs have been described: PEPT1 and PEPT2, with the latter showing higher affinity for a variety of substrates. PEPTs mediate transport of peptide-like drugs, including beta-lactam antibiotics, angiotensin-converting enzyme (ACE) inhibitors and the dipeptide chemotherapeutic drug bestatin . They are located at the brush border membrane.

Amphipathic anionic conjugates such as glucuronide, sulfate and glutathione S-conjugates are believed to be moved by ATP-dependent pumps called GS-X pumps that belong to the ABC (ATP-binding cassette) family of transporters. The ABC family of transport proteins includes MRP, the cystic fibrosis transmembrane regulator (CFTR) and P-gp. GS-X pumps are forms of MRP and two isoforms have been identified: MRP1 at the basolateral membrane, and MRP2 and cMOAT at the apical membrane. These ATP-dependent pumps are able to move conjugated drugs within renal tubular cells either into the urine or back to the ECF. There is also evidence to suggest that cisplatin and daunorubicin may be handled by GS-X transporters . Other MRP homologues have been identified (MRP3, MRP4, MRP5), but their exact drug transporting functions have not been elucidated.

This entry was posted in Kidney and tagged Drug transport; Kidney; P-glycoprotein; Rena drug handling; Transport protein.