Transport of urate and other organic anions by anion exchange in human renal brush-border membrane vesicles

Earlier studies demonstrated that an apical anion exchanger which accepts urate, chloride, aliphatic monocarboxylates, and the aromatic anions, pyrazinoate (PZA) and nicotinate, plays a major role in urate reabsorption in human proximal tubules. In substrate competition studies for transport, we investigated the effect of PZA on 50 mu M [C-14]-urate uptake in exchange of lactate, human brush-border membrane vesicles (BBMV) being loaded with 5 mM lactate. 1 mM PZA cis-inhibited, whereas 0.1 mM PZA cis-stimulated [C-14]-urate uptake in exchange for lactate. Such paradoxical effects suggest the cooperation of two anion exchangers, PZA having more affinity for a 'lactate/anion exchanger' than for a 'urate/anion exchanger'. Apparent K-m of [C-14]-PZA uptake were measured in lactate- or urate-loaded BBMV, and were 0.33 +/- 0.06 and 0.98 +/- 0.44 mM, respectively. Unlike [C-14]-PZA, [C-14]-orotate and [C-14]-nicotinate uptakes were stimulated only to a minor extent in BBMV loaded with lactate. In contrast, cis-inhibition studies in urate-loaded BBMV demonstrated that nicotinate and orotate had similar affinity as PZA for the 'urate/anion exchanger'. Oxalate was shown to have affinity for the 'lactate/anion exchanger', but not for the 'urate/anion exchanger'.