The kidney: UNIQUE TRANSPORTERS EXIST FOR PEPTIDES, CONJUGATES, HYDROPHOBIC DRUGS AND NUCLEOSIDES(2)

HYDROPHOBIC DRUGS AND NUCLEOSIDES(2)

Human prostaglandin transporter (hPGT) appears to be able to mediate the transport of prostaglandins, including PGE1, PGE2, PGD2 and PGF2a. PGT is not limited to the renal tubules and can be found in most tissues. The exact role of PGT in prostaglandin handling is unknown.

By now, most people are familiar with P-gp and its over expression in tumour cells that respond poorly to chemotherapy. Recent data suggest that P-gp plays a role in the renal handling of drugs. Also known as MDR, P-gp is an ATP-dependent, 170-kDa membrane glycoprotein that belongs to the ABC family of transport proteins. Two human isoforms of P-gp have been identified: MDR1 can be found on the apical membrane of renal tubular cells and MDR3 is found mostly in liver cells. Although the exact mechanism of drug translocation by P-gp MDR1 is still speculative, it is known that drug transport is unidirectional into the urine. In a landmark study, ‘knock-out’ mice genetically altered to exclude the MDR1 a gene (the murine equivalent to human MDR1) had plasma concentrations of a variety of drugs two to three times higher than wild-type mice that expressed mdr1a. MDR1-type P-gp has hydrophobic neutral compounds or large hydrophobic compounds with a net positive charge as its substrates. ventolin inhalers

A great deal of current interest in transporter proteins focuses on nucleoside transporters. Two such human proteins have been cloned thus far. Concentrative nucleoside transporter type 1 (CNT1) is a sodium-nucleoside symporter (cotransports sodium and nucleosides) that is selective for pyrimidines as well as transporting adenosine. This transporter has been shown to transport 3′-azido-3′-deoxythymi-dine (AZT) and 2′,3′-dideoxycytidine. The SPNT, originially known as CNT2, is also a sodium-nucleoside cotransporter that appears to be selective for purine nucleosides, as well as transporting uridine. This transporter has been shown to transport dideoxyinosine.

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