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

Characterization of the Uptake of Organic Anion Transporter (OAT) 1 and OAT3 Substrates by Human Kidney Slices.

The activities of renal multispecific organic anion transporters (OATs) 1 and 3 have not been fully evaluated in human kidneys. In the present study, the uptake of some organic anions was characterized in kidney slices from human intact renal cortical tissues: hOAT1 and hOAT3 substrates [p-aminohippurate (PAH) and 2,4-dichlorophenoxyacetate (2,4-D)] and hOAT3 substrates [benzylpenicillin (PCG), dehydroepiandrosterone sulfate (DHEAS), and estrone sulfate (ES)]. Despite large interbatch differences, hOAT1 and hOAT3 mRNA levels correlated well, and there was a good correlation between the uptake of PAH and PCG by kidney slices. The uptake of organic anions by kidney slices was saturable with K(m) values of 31 to 48 muM for PAH, 0.73 to 4.9 muM for 2,4-D, 14 to 90 muM for PCG, and 9.2 to 11 muM for ES. These parameters were comparable with those for hOAT1 and/or hOAT3. The uptake of DHEAS consists of two saturable components with K(m) values of 2.2 to 3.9 and 1300 muM, and the K(m) value of the high-affinity component was close to that for hOAT3. Furthermore, PAH more potently inhibited the uptake of 2,4-D than that of PCG and DHEAS. PCG had a weaker effect on the uptake of PAH and 2,4-D than expected from its K(m) value. Taken together, it is likely that the uptake of PAH and 2,4-D is due to OAT1, and the uptake of PCG and ES and part of DHEAS uptake are due to OAT3 in human kidney slices. Human kidney slices are useful tools for characterizing the renal uptake of drugs.[1]


  1. Characterization of the Uptake of Organic Anion Transporter (OAT) 1 and OAT3 Substrates by Human Kidney Slices. Nozaki, Y., Kusuhara, H., Kondo, T., Hasegawa, M., Shiroyanagi, Y., Nakazawa, H., Okano, T., Sugiyama, Y. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
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