Urate/α-ketoglutarate exchange in avian basolateral membrane vesicles

Abstract

Membrane transport pathways for transcellular secretion of urate across the proximal tubule were investigated in avian kidney. The presence of coupled urate/α-ketoglutarate exchange was investigated in basolateral membrane vesicles (BLMV) by [14C]urate and [α-3H]ketoglutarate flux measurements. An inward Na gradient induced accumulation of α-ketoglutarate of sufficient magnitude to suggest a Na-dicarboxylate cotransporter. An inward Na gradient also induced concentrative accumulation of urate in the presence of α-ketoglutarate but not in its absence, suggesting urate/α-ketoglutarate exchange. α-Ketoglutarate-dependent stimulation of urate uptake was not observed in brush-border membrane vesicles. An outward urate gradient induced concentrative accumulation of α-ketoglutarate. α-Ketoglutarate-coupled urate uptake was specific for α-ketoglutarate, Cl dependent, and insensitive to membrane potential. α-Ketoglutarate-coupled urate uptake was inhibited by increasing p-aminohippurate (PAH) concentrations, and α-ketoglutarate-coupled PAH uptake was observed. α-Ketoglutarate-coupled PAH uptake was inhibited by increasing urate concentrations, and an outward urate gradient induced concentrative accumulation of PAH. These results suggest a Cl-dependent, α-ketoglutarate-coupled anion exchange mechanism as a pathway for active urate uptake across the basolateral membrane of urate-secreting proximal tubule cells.