CLASSICAL AND CHANNEL-LIKE URATE TRANSPORTERS IN RABBIT RENAL BRUSH-BORDER MEMBRANES

The precise mechanism by which urate is transported across rabbit rena l proximal tubule luminal membranes has not been defined. To determine whether urate flux across this membrane represents simple diffusion o r transport on specific carriers, urate uptake was examined in brush b order membrane vesicles that were prepared by a Mg++-aggregation techn ique and then exposed to CuCl2. Na+-independent, voltage sensitive ura te transport was demonstrated in these Cu++-exposed vesicles. Transpor t was trans-stimulated by urate and cis inhibited by pyrazinoic acid a nd oxonate. A small fraction of transported urate and urate in the ext ravesicular fluid was oxidized to allantoin. Kinetic analysis revealed the presence of two kinetically distinct transporters; a channel-like carrier that was inhibited by pyrazinoic acid and oxonate, and a high -affinity, classical, saturable carrier that was inhibited by higher c oncentrations of oxonate. These studies provide the first direct evide nce for carrier-mediated urate transport in rabbit renal brush-border membranes and demonstrate that the rabbit transporter(s) share a numbe r of properties with the urate uniporter in rat proximal tubule cell m embranes.