Solute carrier family 22 member 8 (Organic anion transporter 3) (OAT3)

Solute carrier family 22 member 8, commonly known as Organic anion transporter 3 (OAT3), is a multispecific transporter primarily expressed on the basolateral membrane of renal proximal tubule cells (UniProt: Q8TCC7). It plays a critical role in the active secretion of a wide range of endogenous compounds, such as uric acid and estrone sulfate, as well as numerous clinically important drugs including antibiotics, diuretics, and antivirals (PubMed: 11854143). By mediating the uptake of these substances from the blood into the tubular cells, OAT3 is a key determinant of their renal clearance and systemic exposure (PubMed: 23633525). In the context of pharmacology, OAT3 is a major site for drug-drug interactions; for instance, the inhibition of OAT3 by probenecid can significantly increase the plasma concentration of co-administered drugs like methotrexate, potentially leading to toxicity (FDA Guidance: In Vitro Drug Interaction Studies). Furthermore, OAT3 is involved in the pathophysiology of conditions like hyperuricemia and chronic kidney disease, making it a significant focus for both therapeutic targeting and safety assessment during drug development (PubMed: 28213604). This transporter's activity is essential for maintaining metabolic homeostasis and preventing the accumulation of potentially toxic organic anions in the systemic circulation.

Other names

SLC22A8Organic anion transporter 3Organic acid transporter 3OAT3

Drugs typically act as substrates or inhibitors of OAT3, where inhibition leads to decreased renal clearance and increased systemic exposure of co-administered OAT3 substrates.