Rat Organic Anion Transporter 3 and Organic Anion Transporting Polypeptide 1 Mediate Perfluorooctanoic Acid Transport

Abstract

The mechanism by which perfluorooctanoic acid (PFOA) is transported in the kidney was studied in rats. We hypothesized that some transporters that are expressed in the basolateral and/or brush border membrane of proximal tubular cells mediate the transport of PFOA. Mannitol infusion, which caused an increase in the urine flow rate, significantly increased the renal clearance (CLR) of PFOA in both male and female rats. Feeding a low-phosphate diet that causes an increase in the expression of rat type II sodium-dependent phosphate transporter (Npt2) reduced the CLR in both male and female rats. These suggest that PFOA is reabsorbed in the proximal tubules, and that a phosphate transporter may be responsible for the renal transport of PFOA. The CLR of PFOA in Eisai hyperbilirubinemic rats that lack multidrug resistance-associated protein 2 (MRP2) was not different from that of the wild type, suggesting that MRP2 is not responsible for the renal transport of PFOA. Three candidate transporters, organic anion-transporting polypeptide 1 (oatp1), Npt2, and organic anion transporter 3 (OAT3) were studied to clarify whether these transporters facilitate [14C]PFOA transport in functional studies in Xenopus laevis oocytes. Both oatp1 and OAT3 facilitated [14C]PFOA transport while Npt2 did not. These results suggest that both oatp1 and OAT3 mediate, at least in part, the transport of PFOA in the proximal tubules of rat kidney.