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 |
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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 |