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XB-ART-56010
Drug Metab Pharmacokinet 2019 Aug 01;344:239-246. doi: 10.1016/j.dmpk.2019.04.001.
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Organic anion-transporting polypeptide 1a4-mediated heterogeneous distribution of sulforhodamine-101 in rat hepatic lobules.

Akanuma SI , Kida R , Tsuchiyama A , Tachikawa M , Kubo Y , Hosoya KI .


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It has been known that organic anion-transporting polypeptides (Oatps) involve hepatic transports several organic anionic compounds and drugs. This study aimed to investigate sulforhodamine-101 (SR-101) distribution in the rat liver, determine the molecules responsible for the distribution, and delineate the manner of distribution. After intravenous SR-101 administration, its distribution in frozen rat hepatic sections was examined. SR-101-derived signals were detected in regions around the hepatic central vein (CV), where immunohistochemistry (IHC) indicated high Oatp1a4 expression. The signals decreased with treatment by digoxin, a specific substrate for Oatp1a4. In vitro studies using isolated rat hepatocytes and rat Oatp1a4-expressing Xenopus laevis oocytes have suggested that SR-101 is an Oatp1a4 substrate and is taken up into rat hepatocytes mainly via Oatp1a4. Therefore, results suggested SR-101 zonation because of Oatp1a4 involvement and that Oatp1a4 function is dominant in the region around the hepatic CV in rat hepatic lobules.

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