Human organic anion transporter 1 and Human organic anion transporter 3 (OAT1 and OAT3)

The **human organic anion transporter 1 (OAT1, SLC22A6)** and **human organic anion transporter 3 (OAT3, SLC22A8)** are closely related **membrane transporters** in the kidney, belonging to the solute carrier (SLC22) family[1][3][5]. Both proteins are primarily expressed at the basolateral membrane of proximal tubular cells, where they mediate the uptake of a broad spectrum of endogenous and exogenous organic anions from the blood into renal epithelial cells as the first step in renal secretion and drug elimination[1][3][5]. They operate mainly via an *organic anion–α-ketoglutarate exchange mechanism*, enabling secondary active transport of anionic drugs, toxins, and metabolic waste products[2][3][5]. OAT1/OAT3 are targets for drug-drug interactions (notably inhibition by probenecid), and play important roles in the pharmacokinetics and potential nephrotoxicity of various clinical drugs, especially antivirals (tenofovir, adefovir, cidofovir)[3][4][5]. Dysfunction or pharmacological inhibition of these transporters is implicated in altered drug disposition, toxicity, and disease states such as chronic kidney disease and uremia[3][5]. Structural studies, including recent cryo-EM data, reveal that these proteins operate through complex conformational changes characteristic of the Major Facilitator Superfamily, supporting alternating access of substrates across the membrane[4][5].

Other names

Organic anion transporter 1SLC22A6New Kidney Transporter (NKT)Organic anion transporter 3SLC22A8Organic anion transporter family

Drugs inhibiting OAT1/OAT3: Block renal secretion of target drugs/metabolites, leading to increased plasma levels (e.g., probenecid blocks secretion of uric acid and drug substrates) Drugs utilizing OAT1/OAT3 for elimination: Rely on active transport into renal tubular cells (e.g., tenofovir, adefovir), followed by excretion into urine Exchange mechanism: Secondary active transport via organic anion/dicarboxylate exchanger (primarily α-ketoglutarate)