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

Human organic anion transporters mediate the transport of tetracycline.

The purpose of this study was to elucidate the molecular mechanism for renal tetracycline transport by human organic anion transporters (hOATs) using proximal tubular cells stably expressing hOATs. The cells stably expressing hOAT1, hOAT2, hOAT3 and hOAT4 exhibited a higher amount of [3H]tetracycline uptake compared with mock cells. The apparent Km values for hOAT2-, hOAT3- and hOAT4-mediated tetracycline uptakes were 439.9 +/- 23.0, 566.2 +/- 28.4 and 122.7 +/- 16.0 microM, respectively. Tetracycline significantly inhibited the organic anion uptake by hOAT1, hOAT2 and hOAT4, but not hOAT3. In addition, oxytetracycline, minocycline and doxycycline inhibited the organic anion uptake by hOAT1, whereas oxytetracycline, minocycline but not doxycycline inhibited the organic anion uptake by hOAT2. In contrast, oxytetracycline, minocycline and doxycycline exhibited no significant inhibitory effects on the organic anion uptake by hOAT3 and hOAT4. HOAT1 and hOAT4 mediated the efflux of tetracycline, but hOAT2 and hOAT3 did not. These results suggest that hOAT1, hOAT2 and hOAT3 mediate the basolateral uptake and/or efflux of tetracycline, whereas hOAT4 is responsible for the reabsorption as well as the efflux of tetracycline in the apical side of the proximal tubule. These pharmacological characteristics of hOATs may be significantly related to events associated with the development of tetracycline-induced nephrotoxicity in the human kidney.[1]


  1. Human organic anion transporters mediate the transport of tetracycline. Babu, E., Takeda, M., Narikawa, S., Kobayashi, Y., Yamamoto, T., Cha, S.H., Sekine, T., Sakthisekaran, D., Endou, H. Jpn. J. Pharmacol. (2002) [Pubmed]
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