OCHA

Detailed article on Organic Anion Transporter 3 (OAT3)

Organic Anion Transporter 3 (OAT3) is a protein encoded by the SLC22A8 gene in humans. It is a member of the solute carrier family and plays a crucial role in the renal excretion of endogenous and exogenous organic anions.

Structure

OAT3 is a transmembrane protein that belongs to the SLC22 family of transporters. It is composed of 12 transmembrane domains, which are typical of the major facilitator superfamily. The protein is primarily expressed in the proximal tubule of the kidney, where it is localized to the basolateral membrane of renal tubular cells.

Function

OAT3 functions as an organic anion exchanger, facilitating the uptake of a wide variety of organic anions from the blood into renal tubular cells. This process is essential for the renal clearance of many drugs, toxins, and metabolic waste products. OAT3 has a broad substrate specificity, including:

• Uric acid
• Antibiotics such as penicillin
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Diuretics

The transport activity of OAT3 is driven by the exchange of intracellular dicarboxylates, such as alpha-ketoglutarate, which are recycled by the sodium-dicarboxylate cotransporter.

Clinical Significance

OAT3 plays a significant role in drug-drug interactions and the pharmacokinetics of various medications. Inhibition of OAT3 can lead to altered drug clearance and potential toxicity. Genetic polymorphisms in the SLC22A8 gene can affect the function of OAT3, influencing individual responses to drugs and susceptibility to adverse drug reactions.

Research and Development

OAT3 is a target for research in drug development, particularly in understanding and predicting drug interactions. In vitro studies using cell lines expressing OAT3 are commonly used to assess the potential for drug interactions.

Also see

• Organic Anion Transporter 1
• Organic Anion Transporter 2
• Renal physiology
• Drug metabolism

References

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