Abstract
The organic anion transporters (OAT) have recently been identified. Although the some transport properties of OATs in the kidney have been verified, the regulatory mechanisms for OAT's functions are still not fully understood. The rat OAT1 (rOAT1) transports a number of negatively charged organic compounds between the cells and their extracellular milieu. Caveolin (Cav) also plays a role in membrane transport. Therefore, we investigated the protein-protein interactions between rOAT1 and caveolin-2. In the rat kidney, the expressions of rOAT1 mRNA and protein were observed in both the cortex and the outer medulla. With respect to Cav-2, the expressions of mRNA and protein were observed in all portions of the kidney (cortex < outer medulla = inner medulla). The results of Western blot analysis using the isolated caveolae-enriched membrane fractions or the immunoprecipitates by respective 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 confocal microscopy with immunocytochemistry using 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 oocytes, the [(14)C]p-aminohippurate and [(3)H]methotrexate uptake was slightly, but significantly decreased. The similar results were also observed in rOAT1 over-expressed Chinese hamster ovary cells. These findings suggest that rOAT1 and caveolin-2 are co-expressed in the plasma membrane and rOAT1's function for organic compound transport is upregulated by Cav-2 in the normal physiological condition.
Highlights
The excretion of organic anions, including numerous endogenous and exogenous compounds is mainly performed in the kidney and liver
The rat OAT1 (rOAT1) is a multispecific organic anion transporter that interacts with a variety of organic anions such as p-aminohippurate, β-lactam antibiotics, nonsteroidal anti-inflammatory drugs and diuretics (Sekine et al, 1997; Sweet et al, 1997)
This transporter showed the identical transport characteristics of the classical organic anion transporter that is suggested on the basolateral membrane of the proximal tubule
Summary
The excretion of organic anions, including numerous endogenous and exogenous compounds is mainly performed in the kidney and liver. The rOAT1 is a multispecific organic anion transporter that interacts with a variety of organic anions such as p-aminohippurate, β-lactam antibiotics, nonsteroidal anti-inflammatory drugs and diuretics (Sekine et al, 1997; Sweet et al, 1997). This transporter showed the identical transport characteristics of the classical organic anion transporter that is suggested on the basolateral membrane of the proximal tubule. The caveolins (Cav) have been reported as being important modulating molecules that bind some biologically active proteins. We studied the regulatory effect of caveolin-2 in the function of rOAT1
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