Voltage-driven p-aminohippurate, chloride, and urate transport in porcine renal brush-border membrane vesicles

Abstract.

p-Aminohippurate (PAH) and urate are secreted into the proximal tubule lumen across the brush-border membrane. Here we used brush-border membrane vesicles from pig kidney to study PAH and urate transport. Efflux and influx of [³H]PAH were influenced by K⁺-diffusion potentials indicating electrogenic PAH transport. An outside>inside PAH concentration difference accelerated voltage-sensitive, Na⁺-coupled d-glucose uptake as efficiently as did an outside>inside Cl^– concentration difference, suggesting comparable conductances for PAH and Cl^– in brush-border membrane vesicles. Up to 1 mM of the uricosurics indacrinone, tienilic acid, losartan and probenecid, as well as of the stilbenes, DIDS and SITS, and of the loop diuretics furosemide and bumetanide inhibited voltage-driven PAH uptake, but not, or only slightly, voltage-driven Cl^– uptake. Voltage-driven [¹⁴C]urate uptake, however, was inhibited by 0.1 mM DIDS, 0.2 mM losartan and 0.5 mM probenecid to a similar extent as [³H]PAH uptake. One millimolar pyrazinoic acid, oxonate, xanthine and adenosine inhibited neither [³H]PAH nor [¹⁴C]urate uptake. These results suggest that PAH and urate share an anion conductance which is distinct from the Cl^– conductance and is probably not the same as a recently identified urate channel (Leal-Pinto E et al. J Biol Chem 272:617–625, 1997).