Breast cancer resistant protein (Bcrp, Abcg2) contributes to active urate secretion in mouse and bird renal proximal tubule

Abstract

Unlike most mammals, higher primates, humans, and birds lack uricase and must rely primarily on urinary excretion for the elimination of urate, the intermediate product of purine metabolism. Health complications such as gout, kidney stones, cardiovascular disease, type II diabetes, and metabolic syndrome are associated with hyperuricemia. In the renal proximal tubule, urate is strongly reabsorbed, and the bulk of that excreted is due to active tubular secretion. Following the entry step at the peritubular membrane on organic anion transporters 1 and 3 (OAT1/3), urate is transported to the lumen by a process involving multi‐drug resistance protein 4 (Mrp4, ABCC4). Recently another ATP‐binding cassette family transporter, BCRP, was identified as a possible apical membrane urate efflux transporter. In this study, primary cultures of mouse (mPTCs) and chicken (cPTCs) renal proximal tubule cell monolayers were used to further examine the role of Bcrp in urate secretion. Unidirectional urate flux measurements across mPTCs and cPTCs mounted in Ussing chambers revealed net active urate secretion in both models, and in both, urate secretion was inhibited by luminal exposure to Fumitremorgin C (FTC), a known BCRP inhibitor. Peritubular exposure to FTC did not inhibit urate secretion in mPTCs or cPTCs. Supported by NSF.