The kidney: TRANSPORT MECHANISMS IDENTIFIED WITHIN HUMAN RENAL TUBULAR CELLS(3)

TRANSPORT MECHANISMS IDENTIFIED WITHIN HUMAN RENAL TUBULAR CELLS(3)

Organic anions are able to enter renal tubular cells from the ECF via the dicarboxylate-organic anion exchanger. This entry of anions is coupled with a sodium-dicarboxylate (a-ketoglutarate [a-KG]) exchanger that moves dicarboxy-lates outwards. The process is driven by an inward sodium gradient established by a sodium-potassium ATPase. Ionic compounds such as para-aminohippurate (PAH) and ben-zylpenicillin are substrates for the organic anion transporter (OAT) systems in the proximal renal tubular cells. OAT1 and ROAT1 have been cloned in rats and appear to function as organic anion/dicarboxylate exchangers. PAH (organic anion)-dicarboxy late exchangers have yet to be fully understood in humans, but three cDNAs (complementary DNAs) have been cloned that code for human kidney proteins: OAT1 subtype 1, OAT3 , and ROAT1 (also called para-aminohippurate transporter [PAHT] or OAT1 subtype 2). buy levaquin online

Transporters at the apical (brush border) membrane The apical membrane is on the luminal side of the tubular cell and thus is in contact with urine. At the luminal membrane, organic cations are exchanged with protons from the urine by transporters such as OCTN1 or OCTN2. While OCTN2 is coupled with sodium-independent OAT there also appears to be a sodium-dependent high affinity carnitine transport function. Protons for these exchangers are supplied by an Na+/H+ antiporter and hydrogen-ATPases. Organic anions that have been exchanged with dicarboxylic acid at the basal membranes are believed to be excreted into urine by two postulated mechanisms. Either a potential-sensitive facilitated diffusion system or a hydroxyl ion exchanger may lead to organic anion elimination. Such a hydroxyl exchange pump is believed to be coded by the gene OATP. While a variety of apical anion transport proteins have been cloned, their functions are not well understood. Peptide transporters (PEPTs) involved in the absorption of oligopeptides are also expressed in the apical membrane.

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