It was described as novel kidney transporter because it was almost exclusively expressed in kidney. OAT1 was the next OAT identified, which was initially cloned from a mouse kidney cDNA library ( Lopez-Nieto et al., 1997). Later, novel liver-specific transporter OAT2 was found to be expressed in the liver and kidney at comparable levels and renamed OAT2 because of its close homology with OAT1 and its interaction with organic anions ( Sekine et al., 1998). It was originally called a novel liver-specific transporter because of the dominant mRNA expression in the rat liver ( Simonson et al., 1994). OAT2 was actually the first mammalian OAT to be cloned. The second intriguing feature relates to their principal expression in renal proximal tubule cells (RPTCs) and hepatocytes, the major sites of active compound secretion in the body ( Fig. What is unique about these OATs is their ability to mediate the exchange (extracellular against intracellular) of an impressive number of endogenous molecules, anionic drugs, metabolites, toxins, and signaling molecules with differing molecular composition, polarity, and charge. These transporters are part of the organic ion (solute carrier, SLC) transporter superfamily (i.e., SLC22). Seven human OATs (i.e., OAT1, SLC22A6 OAT2, SLC22A7 OAT3, SLC22A8 OAT4, SLC22A11 OAT7, SLC22A9 OAT10, SLC22A13 and urate anion exchanger 1 (URAT1), SLC22A12) have been identified and characterized functionally ( Burckhardt, 2012 Nigam, 2015 Nigam et al., 2015). It has long been established that an important function of the kidney and liver is the secretion of organic anions into the urine and bile, respectively, and it has been recognized that such secretion is an active and saturable process that can be modulated by competitive inhibitors. We envision that OAT2 will gain more prominence as its expression, substrate, and inhibitor profile is investigated further and compared with other SLCs. The current review focuses on the available and emerging literature describing OAT2. Despite its status as a liver and kidney SLC, tools for assessing its activity and inhibition are lacking, and its role in drug disposition and elimination remains to be defined. Overall, the literature describing OAT2 is rapidly evolving, with numerous publications contradicting each other regarding the transport mechanism, tissue distribution, and transport of creatinine and cGMP, two important endogenous OAT2 substrates. However, OAT2 has received relatively little attention compared with other OATs and solute carriers (SLCs), like organic cation transporters, sodium-dependent taurocholate cotransporting polypeptide, multidrug and toxin extrusion proteins, and organic anion-transporting polypeptides.

As a member of the solute carrier 22A (SLC22A) family, organic anion transporter 2 (OAT2 SLC22A7) is emerging as an important drug transporter because of its expression in both the liver and kidney, two major eliminating organs, and its ability to transport not only a wide variety of xenobiotics but also numerous physiologically important endogenous compounds, like creatinine and cGMP.

Transporter 2