Human Erythrocyte Nucleoside Transporter ENT1 Functions at Ice-cold Temperatures

• TAKANO Mikihisa

  Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University

• KIMURA Eri

  Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University

• SUZUKI Satoshi

  Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University

• NAGAI Junya

  Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University

• YUMOTO Ryoko

  Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University

抄録

  The functionality of human erythrocyte nucleoside transporter ENT1 was examined at ice-cold temperatures (ICT; measured temperature, 0.5-0.7°C) using rightside-out membrane vesicles (ROVs). The uptake of uridine, an ENT1 substrate, showed saturation kinetics and was inhibited by S-(4-nitrobenzyl)-6-thioinosine (NBMPR), a specific ENT1 inhibitor, at both 23°C and ICT. [³H]Uridine uptake was markedly trans-stimulated by preloading ROVs with unlabeled uridine or ribavirin, another ENT1 substrate, and the overshoot phenomenon was observed at ICT. Similarly, [³H]ribavirin uptake was markedly trans-stimulated by unlabeled ribavirin or uridine at ICT. The trans-stimulated uptake of [³H]uridine at ICT was inhibited by ENT1 inhibitors/substrates such as NBMPR, dipyridamole, adenosine, and ribavirin in a concentration-dependent manner. The inhibition of [³H]uridine uptake by NBMPR and dipyridamole at ICT was also observed in intact red blood cells. Like uridine uptake, [³H]D-glucose uptake by ROVs, which is mediated by facilitative glucose transporter GLUT1, was trans-stimulated by unlabeled D-glucose at ICT, and the overshoot phenomenon was observed. In contrast, the ability of ATP-dependent transport of 5-(and-6)-carboxy-2′,7′-dichlorofluorescein via multidrug resistance-associated protein 5 in inside-out membrane vesicles disappeared at ICT. These results clearly indicate that human erythrocyte transporters such as ENT1 function even at very low temperatures near 0°C. The significance of these findings in transporter research is discussed.<br>

収録刊行物

• Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ

  Ｄｒｕｇ　Ｍｅｔａｂｏｌｉｓｍ　ａｎｄ　Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 25 (4), 351-360, 2010

  日本薬物動態学会

キーワード

• erythrocyte
• membrane vesicles
• nucleoside transporter
• uridine
• ribavirin
• trans-stimulation effect
• glucose transporter

詳細情報

• CRID: 1390282680157658240
• NII論文ID: 10027583239
• NII書誌ID: AA1162652X
• DOI: 10.2133/dmpk.dmpk-09-rg-099
• ISSN: 18800920
• ISSN: 13474367
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715300422?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715300422?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2011117950
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • CiNii Articles
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