Figure 2

Effects of URAT1, GLUT9, and ABCG2 on urate anion disposition by the renal proximal tubule epithelial cell and inhibitory effects of the uricosurics probenecid and benzbromarone on renal urate reabsorption by inhibition of both URAT1 and GLUT9. The schematic summarizes the effects of the uricosurics probenecid and benezbromarone on urate handling in the renal proximal tubule epithelial cell by the URAT1 (SLC22A12) and GLUT9 (SLC2A9) transporters identified as linked with serum urate levels and gout susceptibility in genetic studies, including recent genome-wide association studies. Urate reabsorption at the apical membrane, which interfaces with the tubule lumen, is mediated in large part by the anion exchange function of URAT1. At the basolateral membrane, the hexose transport facilitator GLUT9 electrogenically transports urate anion into the peritubular interstitium, where urate is reabsorbed into the circulation. Recent genome-wide association studies and functional genomics analyses have also uncovered a substantial role for ABCG2 in secretion of urate into the proximal tubule lumen. The depicted model is a simplification, since other molecules that affect urate disposition in the proximal tubule and distally in the nephron are not depicted here, and effects of certain other drugs on renal urate disposition by inhibiting URAT1 or GLUT9 or other transporters are not represented. ABCG, ATP binding cassette sub-family G; GLUT, glucose transporter; URAT1, urate transporter 1.