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

• 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

Abstract

  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 [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 K_m 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.<br>

Journal

• Drug Metabolism and Pharmacokinetics

  Drug Metabolism and Pharmacokinetics 23 (4), 285-292, 2008

  The Japanese Society for the Study of Xenobiotics

Keywords

• methyltetrahydrofolate (MTF)
• carrier-mediated transport
• inner blood-retinal barrier
• reduced folate carrier 1 (RFC1)

Details

• CRID: 1390001205181072896
• NII Article ID: 10021956423
• NII Book ID: AA1162652X
• DOI: 10.2133/dmpk.23.285
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715301981?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715301981?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2009059460
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed