Involvement of Reduced Folate Carrier 1 in the inner Blood-Retinal Barrier Transport of Methyltetrahydrofolate

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著者

    • HOSOYA Ken-ichi
    • Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
    • FUJITA Keiko
    • Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
    • TACHIKAWA Masanori
    • Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama

抄録

  The purpose of this study was to elucidate the mechanism of methyltetrahydrofolate (MTF) transport at the inner blood-retinal barrier (inner BRB). The characteristics and function of MTF transport at the inner BRB were examined using a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2) as an in vitro model of the inner BRB. The [<sup>3</sup>H]MTF uptake by TR-iBRB2 cells increased with lowering extracellular pH and was Na<sup>+</sup>- and Cl<sup>-</sup>-independent. The [<sup>3</sup>H]MTF uptake was concentration-dependent with a K<sub>m</sub> of 5.1 μM. This process was inhibited by reduced folate carrier 1 (RFC1) substrates, such as methotrexate and formyltetrahydrofolate, in a concentration-dependent manner with an IC<sub>50</sub> of 8.7 and 2.8 μM, respectively, suggesting that RFC1 mediates MTF uptake in TR-iBRB2 cells. Although both RFC1 and proton-coupled folate transporter (PCFT) mRNA, which are pH-sensitive folate transporters, are expressed in TR-iBRB2 cells and isolated rat retinal vascular endothelial cells, the expression level of RFC1 mRNA was 83- and 49-fold greater than that of PCFT, respectively. Taken together, the above findings are consistent with the involvement of RFC1 in the inner BRB transport of MTF.<br>

収録刊行物

  • Drug metabolism and pharmacokinetics  

    Drug metabolism and pharmacokinetics 23(4), 285-292, 2008-08-25 

    The Japanese Society for the Study of Xenobiotics

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各種コード

  • NII論文ID(NAID)
    10021956423
  • NII書誌ID(NCID)
    AA1162652X
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13474367
  • データ提供元
    CJP書誌  J-STAGE 
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