Involvement of reduced folate carrier 1 in the inner blood-retinal barrier transport of methyltetrahydrofolate

Ken Ichi Hosoya, Keiko Fujita, Masanori Tachikawa

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


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 (TRiBRB2) as an in vitro model of the inner BRB. The [3H]MTF uptake by TR-iBRB2 cells increased with lowering extracellular pH and was Na+- and Cl+-independent. The [3H]MTF uptake was concentration-dependent with a Km 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 IC50 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.

Original languageEnglish
Pages (from-to)285-292
Number of pages8
JournalDrug metabolism and pharmacokinetics
Issue number4
Publication statusPublished - 2008


  • Carrier-mediated transport
  • Inner blood-retinal barrier
  • Methyltetrahydrofolate (MTF)
  • Reduced folate carrier 1 (RFC1)

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)


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