Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Bahn, A. et al.

Bahn, Ebbinghaus, Ebbinghaus, Ponimaskin, Fuzesï, Burckhardt, Hagos,

Expression studies and functional characterization of renal human organic anion transporter 1 isoforms.

The human organic anion transporter 1 (hOAT1) facilitates the basolateral entry of organic anions such as endogenous metabolites, xenobiotics, and drugs into the proximal tubule cells. In the present study we investigated the general occurrence of hOAT1 isoforms in the kidneys and performed functional characterizations. Kidney specimens of 10 patients were analyzed by reverse transcription-polymerase chain reaction. We detected hOAT1-2 as the main transcript in almost all patients, and weak transcripts of hOAT1-1, hOAT1-3, and hOAT1-4 in many of them. An evaluation of the renal distribution showed all four mRNAs mostly restricted to the cortex. Western blot analysis of membrane fractions from two kidney specimens yielded two bands corresponding to the observed mRNA expression, suggesting hOAT1-3 and hOAT1-4 to be expressed on the protein level in vivo. This observation is further supported by immunofluorescence analyses of all four cloned hOAT1 isoforms transiently transfected in COS 7 cells. Functional characterizations did not show any transport activity of hOAT1-3 and hOAT1-4 for the tested substrates. Cotransfection studies of each of them with hOAT1-1 did not alter fluorescein uptake indicating no regulatory impact of these isoforms. Further functional comparisons of hOAT1-1 and hOAT1-2 in fluorescein uptake studies exhibited almost identical affinities for fluorescein with Michaelis constants of 11.6 +/- 3.7 microM (hOAT1-1) and 11.9 +/- 6.4 microM (hOAT1-2), and similar sensitivities to inhibition by p-aminohippurate [IC(50): 16 microM (hOAT1-1), 10 microM (hOAT1-2)], urate [IC(50): 440 microM (hOAT1-1), 385 microM (hOAT1-2)], and furosemide (IC(50): 14 microM (hOAT1-1), 20 microM (hOAT1-2)], implying functional equivalence.[1]

References

Expression studies and functional characterization of renal human organic anion transporter 1 isoforms. Bahn, A., Ebbinghaus, C., Ebbinghaus, D., Ponimaskin, E.G., Fuzesï, L., Burckhardt, G., Hagos, Y. Drug Metab. Dispos. (2004) [Pubmed]

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