Medication for pregnant women based on 'barrier transition' behavior in feto-placental circulation

• Project/Area Number: 15K15007
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Keio University
• Principal Investigator: Tomi Masatoshi 慶應義塾大学, 薬学部(芝共立), 教授 (30334717)
• Co-Investigator(Kenkyū-buntansha): 西村 友宏 慶應義塾大学, 薬学部(芝共立), 講師 (40453518)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 胎盤関門 / miRNA

Outline of Final Research Achievements

We have clarified the developmental change in the placental transporters such as glucose transporter 1 (GLUT1) and monocarboxylate transporter 1 (MCT1), while the expressions of ABC transporters such as MDR1 and BCRP were unchanged during pregnancy. We also found a placenta-derived miRNA which may work for maturation of both placental and blood-brain barrier. These observations are helpful for examining the interorgan network in the fetoplacental circulation for establishing and managing barriers in the placenta and the brain.

Research Products

• [Int'l Joint Research] カリフォルニア大学サンフランシスコ校(米国)
• [Journal Article] Cellular uptake of levocetirizine by Organic Anion Transporter 4 (2017)
  • Author(s): Noguchi S, Nishimura T, Mukaida S, Benet LZ, Nakashima E, Tomi M
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 印刷中 Issue: 9 Pages: 2895-2898
  • DOI: 10.1016/j.xphs.2017.03.026
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Co-localization of microsomal prostaglandin E synthase-1 with cyclooxygenase-1 in layer II of murine placental syncytiotrophoblasts (2017)
  • Author(s): M. Inagaki, T. Nishimura, S. Akanuma, T. Nakanishi, M. Tachikawa, I. Tamai, K. Hosoya, E. Nakashima, M. Tomi
  • Journal Title: Placenta Volume: 53 Pages: 76-82
  • DOI: 10.1016/j.placenta.2017.04.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Contribution of equilibrative nucleoside transporter (ENT) 2 to fluorouracil transport in rat placental trophoblast cells (2017)
  • Author(s): A. Takagi, T. Nishimura, T. Akashi, M. Tomi, E. Nakashima
  • Journal Title: Drug Metab. Pharmacokinet. Volume: 32 Issue: 2 Pages: 151-156
  • DOI: 10.1016/j.dmpk.2016.12.001
  • NAID: 210000176253
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Contributions of system A subtypes to α-methylaminoisobutyric acid uptake by placental microvillous membranes of human and rat. (2017)
  • Author(s): Takahashi Y, Nishimura T, Maruyama T, Tomi M, Nakashima E
  • Journal Title: Amino Acids. Volume: 49 Issue: 4 Pages: 795-803
  • DOI: 10.1007/s00726-017-2384-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Layer II of placental syncytiotrophoblasts expresses MDR1 and BCRP at the apical membrane in rodents (2016)
  • Author(s): T. Akashi, T. Nishimura, Y. Takaki, M. Takahashi, B.C. Shin, M. Tomi, E. Nakashima
  • Journal Title: Reprod. Toxicol. Volume: 65 Pages: 375-381
  • DOI: 10.1016/j.reprotox.2016.09.002
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Hypotaurineおよびその供給因子の胎盤組織内分布 (2017)
  • Author(s): 斉藤慶、西村友宏、中島恵美 、登美斉俊
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2017-03-24
• [Presentation] 胎盤を介した胎児からのクレアチニン排出輸送機構の解析 (2017)
  • Author(s): 山下稔貴、西村友宏、中島恵美、登美斉俊
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2017-03-24
• [Presentation] SLC6Aファミリーによるヒポタウリン輸送と酸化ストレスに対する細胞保護作用 (2016)
  • Author(s): 西村友宏、樋口慧、中島恵美、登美斉俊
  • Organizer: 第38回生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 名古屋市立大学大学院薬学研究科（愛知県名古屋市）
  • Year and Date: 2016-11-17
• [Presentation] Syncytiotrophoblast layer 2 expresses MDR1 and BCRP efflux transporters in rodent placenta. (2015)
  • Author(s): Tomi M, Akashi T, Takaki Y, Nishimura T, Nakashima E.
  • Organizer: International Federation of Placenta Associations 2015
  • Place of Presentation: Brisbane (Australia)
  • Year and Date: 2015-09-08
  • Int'l Joint Research
• [Presentation] げっ歯類胎盤関門におけるMDR1およびBCRPの局在とヒトとの種差 (2015)
  • Author(s): 明石知也, 西村友宏, 高木良也, 登美斉俊, 中島恵美.
  • Organizer: 第10回トランスポーター研究会年会
  • Place of Presentation: 慶應義塾大学薬学部（東京都港区）
  • Year and Date: 2015-06-20
• [Presentation] 関門トランスポーターによる薬物組織分布制御機構の研究 (2015)
  • Author(s): 登美斉俊
  • Organizer: 日本薬剤学会第30年会
  • Place of Presentation: 長崎ブリックホール(長崎県長崎市）
  • Year and Date: 2015-05-21
  • Invited