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The organic anion transporters (OAT) have re-cently been identified. Although the some trans-port properties of OATs in the kidney have been verified, the regulatory mechanisms for OAT's OAT1 (rOAT1) transports a number of negatively charged organic compounds between the cels and their extracelular milieu. Caveolin (Cav) also plays a role in membrane transport. Therefore, we investigated the protein-protein interactions betwen rOAT1 and caveolin-2. In the rat kidney, the expresions of rOAT1 mRNA and protein were observed in both the cortex and the outer medula. With respect to Cav-2, the expressions of mRNA and protein were observed in al portions of the kidney (cortex< outer medula = inner medulla). The results of Western blot ana-lysis using the isolated caveolae-enriched mem-brane fractions or the imunoprecipitates by re-spective antibodies from the rat kidney showed that rOAT1 and Cav-2 co-localized in the same fractions and they formed complexes each other. These results were confirmed by performing con-focal microscopy with imunocytochemistry us-ing the primary cultured renal proximal tubular cells. When the synthesized cRNA of rOAT1 along with the antisense oligodeoxynucleotides of Xenopus Cav-2 were co-injected into Xenopus ocytes, the [14C]p-aminohippurate and [3H]me-thotrexate uptake was slightly, but significantly decreased. The similar results were also ob-served in rOAT1 over-expressed Chinese hamster ovary cels. These findings sugest that rOAT1 and caveolin-2 are co-expressed in the plasma membrane and rOAT1's function for organic com-pound transport is upregulated by Cav-2 in the normal physiological condition.

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