ヒグチ ケイ   Higuchi Kei
  樋口 慧
   所属   東邦大学  薬学部 薬学科
   職種   准教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Expression and Functional Characterization of Drug Transporters in Brain Microvascular Endothelial Cells Derived from Human Induced Pluripotent Stem Cells.
掲載誌名 正式名:Molecular pharmaceutics
ISSNコード:1543-8384
掲載区分国外
巻・号・頁 15(12),pp.5546-5555
著者・共著者 Toshiki Kurosawa,Yuma Tega,Kei Higuchi,Tomoko Yamaguchi,Takashi Nakakura,Tatsuki Mochizuki,Hiroyuki Kusuhara,Kenji Kawabata,Yoshiharu Deguchi
発行年月 2018/12/03
概要 Brain microvascular endothelial cells derived from human induced pluripotent stem cells (hiPS-BMECs) have been proposed as a new blood-brain barrier model, but their transport function has not been fully clarified. Therefore, in this study, we investigated the gene expression and function of transporters in hiPS-BMECs by means of quantitative reverse transcription-PCR, in vitro transcellular transport studies, and uptake experiments. mRNAs encoding ABC and SLC transporters, such as BCRP, MCT1, CAT1, and GLAST, were highly expressed in hiPS-BMECs. Transcellular transport studies showed that prazosin, [14C]l-lactate, [3H]l-arginine, and [3H]l-glutamate (substrates of BCRP, MCT1, CAT1, and GLAST, respectively) were transported asymmetrically across the hiPS-BMEC monolayer. Substrates of LAT1, OCTN2, CAT1, GLAST, MCT1, and proton-coupled organic cation (H+/OC) antiporter were taken up by hiPS-BMECs in a time-, temperature-, and concentration-dependent manner, and the uptakes were markedly decreased by inhibitors of the corresponding transporter. These results indicate that hiPS-BMECs express multiple nutrient and drug transporters.
DOI 10.1021/acs.molpharmaceut.8b00697
PMID 30376629