Uricosuric agents such as probenecid lower serum uric acid by acting on a specific transporter at the proximal tubule. Which transporter is the established target of probenecid and lesinurad?

• A ABCG2, the intestinal ATP-dependent urate efflux pump
• B GLUT9, the basolateral glucose-fructose transporter that secretes urate into blood
• C OCTN2, the carnitine transporter that cotransports urate into tubular cells
• D URAT1 (SLC22A12), the apical urate-anion exchanger responsible for urate reabsorption ✓

Explanation

Probenecid and lesinurad inhibit URAT1 (SLC22D12) on the apical membrane of proximal tubular cells. Blocking this exchange transporter prevents urate reabsorption from the tubular lumen, increasing urinary urate excretion and lowering serum levels. GLUT9 mediates basolateral urate exit and is a genetic gout locus but not the drug target. ABCG2 handles intestinal urate excretion, and OCTN2 transports carnitine, not urate. Indian exam convention classifies probenecid firmly among uricosurics.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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