Abstract
SLC17A3 belongs to the type I sodium-phosphate transporter (NPT) family SLC17, but the substrates for its gene product NPT4 remain unknown. In 2008, a genome-wide association study by Deghan et al. identified that SNPs near SLC17A3 correlates with blood urate levels. Recently, we found that NPT4, detected at the apical side of renal proximal tubules, is a multispecific voltage-driven efflux transporter for organic anions such as para-aminohippurate (PAH) and urate using the Xenopus oocyte expression system. In this study, we further investigated the transport properties of NPT4. We prepared NPT4 cRNA by in vitro transcription and the cRNA was microinjected into oocytes.2-3 days after injection, we measured the uptake of radiolabelled PAH and urate. For the measurement of their efflux, we directly injected these agents into oocytes and calculated the efflux value by measuring the RI activities the supernatant and oocyte lysate, respectively. The alteration of intracellular pH affected both PAH and urate uptake via NPT4, while alteration of extracellular pH did not affect their efflux. Consistent with our previous data, extracellular Na+ replacement with K+ increased NPT4-mediated PAH and urate uptake, which was observed only when the extracellular K+ concentration exceeded 50 mM. Thus, the properties of NPT4-mediated urate transport appeared very similar to those of NPT4-mediated PAH transport, suggesting that NPT4 utilizes the same substrate binding site for both PAH and urate. Drug-induced hyperuricemia may be caused by the interaction of anionic drugs and urate at the same binding site of NPT4.
