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OAT2 (SLC22A7)

Molecular structure and Tissue distribution
The SLC22A7 gene for human OAT2 is located on chromosome 6p21.1. The secondary structure analysis of the hOAT2 protein predicted 12 transmembrane helices with the N- and C-termini located at the cytosolic side of the plasma membrane. While other OATs are primarily expressed in the kidney, Northern blot analysis indicated that hOAT2 mRNA is predominantly expressed in the liver and only with lower levels in the kidney. Immunolocalisation of hOAT2 showed the protein in the basolateral membrane of proximal tubules, while in the liver hOAT2 is assumed in the sinusoidal membrane of hepatocytes.
Human OAT2 has two splice variants with NCBI accession NM_006672 and NM_153320. The difference between the two variants is a 6-bp insertion between exons 1 and 2 in the NM_153320 gene, which results in a loss of function.

Interaction of OAT2 with endogenous compounds and drugs
Human OAT2 interacts with a wide range of nucleobases, nucleosides and nucleotides. The cyclic nucleotide cGMP (Km=88 µM) seems to be the preferred substrate besides orotic acid, GMP and 2-deoxyguanosine.
Drugs interacting with hOAT2 are e.g. the diuretics bumetanide and cyclothiazide, the antineoplastic drug methotrexate and the NSAIDs diclofenac, indomethacin, mefenamate and piroxicam.

 

Figure 1 Concentration dependent OAT2 mediated cGMP uptake Figure 2 Inhibition of OAT2 mediated cGMP uptake by indomethacin


 

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