Liver, Pancreas, and Biliary TractLocalization and function of the organic anion–transporting polypeptide Oatp2 in rat liver☆,☆☆
Section snippets
Chemicals
[Prolyl-3,4(n)-3H]BQ-123 (43.0 Ci/mmol) was obtained from Amersham Life Science (Amersham, England). Unlabeled BQ-123 was purchased from Research Biochemicals Internet (Natick, MA). [3H]LTC4 (165 Ci/mmol), [3H]dehydroepiandrosterone sulfate (DHEAS) (16 Ci/mmol), [3H]α-ketoglutarate (280.8 Ci/mmol), and [3H]p-aminohippurate (5 Ci/mmol) were purchased from DuPont–New England Nuclear (Boston, MA). [14C] Dinitrophenylglutathione (10 mCi/mmol) was synthesized as described by Ishikawa.12 Uridine
Cellular and subcellular distribution of Oatp2
The reactivity of the polyclonal antibodies with basolateral rat liver plasma membrane proteins is illustrated in Figure 1.
Discussion
The present study shows a unique compartmentalized basolateral expression of Oatp2 in parenchymal liver cells of normal rats on both the mRNA (Figure 2) and protein (Fig. 3, Fig. 3) levels. Recently, other investigators reported similar results on the immunohistochemical level.24 Our data suggest that Oatp2 is not expressed in the periportal proliferative compartment and requires either aging and differentiation of hepatocytes within the individual liver cell plates27 and/or is dependent on
Acknowledgements
The authors thank Dr. D. Keppler, Deutsches Krebsforschungszentrum, Abteilung Tumorbiochemie, Heidelberg, Germany, for making the radiolabeled bilirubin monoglucuronide available.
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2014, Toxicology in VitroCitation Excerpt :On the contrary, pravastatin did not alter the uptake rate of bilirubin. This can be attributed to the fact that pravastatin is a substrate for more Oatps, namely, Oatp1a1 and Oatp1b2 but not for Oatp1a4 (Bergwerk et al., 1996; Hsiang et al., 1999; Sasaki et al., 2004), which is involved in the uptake of bilirubin (Reichel et al., 1999; Roy Chowdhury et al., 2001). Moreover, administration of pravastatin (5 mg/kg) significantly increased the expression level of Oatp1a4 in vivo in rat liver (Kolouchova et al., 2011).
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Address requests for reprints to: Peter J. Meier-Abt, M.D., Division of Clinical Pharmacology and Toxicology, Department of Internal Medicine, University Hospital, CH-8091 Zurich, Switzerland. e-mail: [email protected]; fax: (41) 1-255-4411.
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Supported by the Swiss National Science Foundation (grants 31-045536.95 to P.J.M. and 31-045677.95 to B.H.); the Olga Mayenfisch Foundation (to B.G.), Zurich, Switzerland; the Cloetta Foundation (to B.H.), Zurich, Switzerland; the Deutsche Forschungs- gemeinschaft (SFB 601/A2), Heidelberg, Germany; and the Doerenkamp Foundation (to C.R.), Germany. Dr. van Montfoort was supported by an Ubbo Emmius scholarship from the University of Groningen, The Netherlands. Dr. Kamisako was supported by the Alexander von Humboldt Foundation, Bonn, Germany.