Transport Characteristics of Ribavirin in Human Erythrocyte Membrane Vesicles

• Yumoto Ryoko

  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

• Imaoka Hiroaki

  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

• Takano Mikihisa

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

抄録

Transport characteristics of ribavirin in human erythrocytes were evaluated using rightside-out membrane vesicles (ROVs) prepared from fresh blood, and compared with those in intact erythrocytes. [3H]Ribavirin uptake by ROVs at 23 °C was fairly rapid, and reached equilibrium at about 30 sec. The uptake of [3H]ribavirin by ROVs showed saturation kinetics with the Km value of 1.9 mM. The uptake by ROVs was inhibited by uridine (a typical substrate of equilibrative nucleoside transporter ENT1), S-(4-nitrobenzyl)-6-thioinosine (a specific inhibitor of ENT1), and dipyridamole (an inhibitor of ENT1). These characteristics of [3H]ribavirin transport in ROVs were similar to those observed in intact erythrocytes, though the affinity of [3H]ribavirin to the transport system and sensitivity to various inhibitors were lower in ROVs. Next, the interaction of ribavirin with ATP-dependent efflux transporters was evaluated using inside-out membrane vesicles (IOVs). Ribavirin weakly inhibited ATP-dependent uptake of methotrexate by multidrug resistance-associated protein (MRP) 4, but not the uptake of 5-(and 6)-carboxy-2', 7'-dichlorofluorescein by MRP5, by IOVs. However, ATP-dependent uptake of [3H]ribavirin by IOVs was not observed. These results suggest that ribavirin is transported by ENT1 across human erythrocyte membranes, while ATP-dependent efflux transporters would not be involved in ribavirin transport.

収録刊行物

• 膜

  膜 35 (6), 297-304, 2010

  日本膜学会

キーワード

• ribavirin
• erythrocyte membranes
• rightside-out vesicles
• equilibrative nucleoside transporter
• efflux transporter

詳細情報

• CRID: 1390282681398700928
• NII論文ID: 10027742018
• NII書誌ID: AN0023215X
• DOI: 10.5360/membrane.35.297
• ISSN: 18846440
• ISSN: 03851036
• NDL書誌ID: 10914118
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10914118
• Web Site: https://search.jamas.or.jp/link/ui/2011164806
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可