DUDAS, P.L.*; BRAUN, E.J.; PARKER, S.L.; RENFRO, J.L.: Urate Transport by Chick (Gallus gallus) Renal Proximal Tubule Epithelium

Birds excrete uric acid (UA) as the major excretory end product of nitrogen metabolism. Others have shown that the renal proximal tubule is the site of UA secretion. In chickens transport of UA across the proximal tubule peritubular membrane appears to be via the classical organic anion (OA) transport system in addition to a mechanism specific for UA alone. Previous studies indicated both passive diffusion and carrier-mediated anion exchange of UA across the luminal membrane. We examined transepithelial UA transport in monolayers of chick proximal tubule cells in primary culture (PTCs). Ussing chambers were used to measure ¹⁴C-UA secretory, reabsorptive and net fluxes as well as transepithelial electrical properties. Probenecid (1 mM), a competitive inhibitor of the OA secretory system, significantly (P < 0.05) inhibited the UA secretory flux ~ 70% and completely abolished net secretion. Reabsorptive flux was unaffected. Glutarate (1 mM), previously shown at high concentrations to be a competitive inhibitor of OA transport, added to the peritubular side of the tissue, significantly (P < 0.05) decreased net transepithelial UA secretion ~ 72%. Presumed hyperpolarization of the luminal membrane by removal of luminal glucose stimulated UA transport. Exposure of the luminal membrane to the very selective MRP2 inhibitor, MK571 (20 µM), dramatically decreased both the UA secretory flux and net secretion. These data indicate that UA secretion in this in vitro system is mediated by the classical OA transport system in the peritubular membrane and a combination of potential driven transport and active transport by MRP2 in the luminal membrane. Supported by NSF.