Transcellular transport of organic anions across a double-transfected Madin-Darby canine kidney II cell monolayer expressing both human organic anion-transporting polypeptide (OATP2/SLC21A6) and Multidrug resistance-associated protein 2 (MRP2/ABCC2).

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  • Author(s): Sasaki M;Sasaki M; Suzuki H; Ito K; Abe T; Sugiyama Y
  • Source:
    The Journal of biological chemistry [J Biol Chem] 2002 Feb 22; Vol. 277 (8), pp. 6497-503. Date of Electronic Publication: 2001 Dec 17.
  • Publication Type:
    Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Print ISSN: 0021-9258 (Print) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Membrane Transport Proteins*; Estradiol/*analogs & derivatives ; Estrone/*analogs & derivatives ; Liver-Specific Organic Anion Transporter 1/*metabolism ; Multidrug Resistance-Associated Proteins/*metabolism ; Taurolithocholic Acid/*analogs & derivatives; Animals ; Biological Transport ; Cell Culture Techniques/methods ; Cell Line ; Cell Membrane/metabolism ; Dehydroepiandrosterone Sulfate/metabolism ; Dogs ; Estradiol/metabolism ; Estrone/metabolism ; Humans ; Kidney ; Kinetics ; Liver-Specific Organic Anion Transporter 1/genetics ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/genetics ; Rats ; Recombinant Proteins/metabolism ; Taurolithocholic Acid/metabolism ; Transfection
    • Abstract:
      Human organic anion transporting polypeptide 2 (OATP2/SLC21A6) and multidrug resistance-associated protein 2 (MRP2/ABCC2) play important roles in the vectorial transport of organic anions across hepatocytes. In the present study, we have established a double-transfected Madin-Darby canine kidney (MDCK II) cell monolayer, which expresses both OATP2 and MRP2 on basal and apical membranes, respectively. The basal-to-apical transport of 17 beta estradiol 17 beta-d-glucuronide (E(2)17 beta G), pravastatin, and leukotriene C(4) (LTC(4)), which are substrates of OATP2 and MRP2, was significantly higher than that in the opposite direction in the double-transfected cells. Such vectorial transport was also observed for taurolithocholate sulfate, which is transported by rat oatp1 and Mrp2. The K(m) values of E(2)17 beta G and pravastatin for the basal-to-apical flux were 27.9 and 24.3 microm, respectively, which were comparable with those reported for OATP2. Moreover, the MRP2-mediated export of E(2)17 beta G across the apical membrane was not saturated. In contrast, basal-to-apical transport of estrone-3-sulfate and dehydroepiandrosterone sulfate, which are significantly transported by OATP2, but not by MRP2, was not stimulated by MRP2 expression. The double-transfected MDCK II monolayer expressing both OATP2 and MRP2 may be used to analyze the hepatic vectorial transport of organic anions and to screen the transport profiles of new drug candidates.
    • Accession Number:
      0 (ABCC2 protein, human)
      0 (Liver-Specific Organic Anion Transporter 1)
      0 (Membrane Transport Proteins)
      0 (Multidrug Resistance-Associated Protein 2)
      0 (Multidrug Resistance-Associated Proteins)
      0 (Recombinant Proteins)
      15324-65-9 (taurolithocholic acid 3-sulfate)
      1806-98-0 (estradiol-17 beta-glucuronide)
      2DI9HA706A (Estrone)
      4TI98Z838E (Estradiol)
      516-90-5 (Taurolithocholic Acid)
      57B09Q7FJR (Dehydroepiandrosterone Sulfate)
      QTL48N278K (estrone sulfate)
      Y49M64GZ4Q (multidrug resistance-associated protein 1)
    • Publication Date:
      Date Created: 20011219 Date Completed: 20020424 Latest Revision: 20211203
    • Publication Date:
      20221213
    • Accession Number:
      10.1074/jbc.M109081200
    • Accession Number:
      11748225