Urate/ -ketoglutarate exchange in avian basolateral membrane vesicles

Grassl, Steven M. Urate/ -ketoglutarate exchange in avian basolateral membrane vesicles. Am J Physiol Cell Physiol 283: C1144–C1154, 2002. First published June 13, 2002; 10.1152/ajpcell.00379.2001.—Membrane transport pathways for transcellular secretion of urate across the proximal tubule were investigated in avian kidney. The presence of coupled urate/ -ketoglutarate exchange was investigated in basolateral membrane vesicles (BLMV) by [14C]urate and [ -3H]ketoglutarate flux measurements. An inward Na gradient induced accumulation of -ketoglutarate of sufficient magnitude to suggest a Na-dicarboxylate cotransporter. An inward Na gradient also induced concentrative accumulation of urate in the presence of -ketoglutarate but not in its absence, suggesting urate/ -ketoglutarate exchange. -Ketoglutarate-dependent stimulation of urate uptake was not observed in brush-border membrane vesicles. An outward urate gradient induced concentrative accumulation of -ketoglutarate. -Ketoglutarate-coupled urate uptake was specific for -ketoglutarate, Cl dependent, and insensitive to membrane potential. -Ketoglutarate-coupled urate uptake was inhibited by increasing p-aminohippurate (PAH) concentrations, and -ketoglutarate-coupled PAH uptake was observed. -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, -ketoglutarate-coupled anion exchange mechanism as a pathway for active urate uptake across the basolateral membrane of urate-secreting proximal tubule cells.