Tomi, Masatoshi

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 薬剤学講座 (Shiba-Kyoritsu)

Position

Professor

E-mail Address

E-mail address

Related Websites

External Links

Career 【 Display / hide

  • 2001.04
    -
    2005.09

    Assistant Professor, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University

  • 2005.10
    -
    2006.03

    Assistant Professor, Faculty of Pharmaceutical Sciences, University of Toyama

  • 2006.04
    -
    2008.12

    Postdoctoral Fellow, David Geffen School of Medicine, University of California, Los Angeles (UCLA)

  • 2009.01
    -
    2011.03

    Senior Assistant Professor, Faculty of Pharmacy, Keio University

  • 2011.04
    -
    2016.03

    Associate Professor, Faculty of Pharmacy, Keio University

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Academic Background 【 Display / hide

  • 1998.03

    Tohoku University, Faculty of Pharmaceutical Science, 薬学科

    University, Graduated

  • 2000.03

    Tohoku University, Graduate School, Division of Pharmaceutical Sciences, 分子生命薬学専攻

    Graduate School, Completed, Master's course

  • 2001.03

    Tohoku University, Graduate School, Division of Pharmaceutical Sciences, 生命薬学専攻

    Graduate School, Withdrawal before completion, Doctoral course

Academic Degrees 【 Display / hide

  • Ph.D.(Pharmaceutical Sciences), Tohoku University, Dissertation, 2004.01

 
 

Books 【 Display / hide

  • 胎盤関門の構造・機能と薬物の胎児への移行, IN: スタンダード薬学シリーズⅡ 6 医療薬学 Ⅵ. 薬の生体内運命, 日本薬学会 (編)

    際吉道, 登美斉俊, 東京化学同人, 2016.12

    Scope: 63-65

  • 血液胎盤関門, IN: 薬剤学実験法必携マニュアル - Pharmaceutical Scientistのために, 日本薬剤学会出版委員会 (編)

    登美斉俊, 西村友宏, 南江堂, 2014.04

    Scope: 138-145

  • 薬の運命, IN: 薬の生体内運命 改訂5版, 中島恵美(編)

    登美斉俊, ネオメディカル, 2013.03

    Scope: 12-18

  • 薬の体内動態, IN: 今日のOTC薬 改訂第2版, 中島恵美, 伊藤明彦 (編)

    登美斉俊, 南江堂, 2012.04

    Scope: 628-631

  • Molecular mechanisms of the inner blood-retinal barrier transporters, IN: Ocular Transporters in Ophthalmic Diseases and Drug Delivery, J. Tombran-Tink and C.J. Barnstable (Eds.).

    Tomi Masatoshi, Hosoya Ken-ichi., Humana Press-Springer, 2008.01

    Scope: 139-156

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Papers 【 Display / hide

  • IFPA meeting 2018 workshop report II: Abnormally invasive placenta; inflammation and infection; preeclampsia; gestational trophoblastic disease and drug delivery

    Albrecht C., Chamley L., Charnock-Jones D., Collins S., Fujiwara H., Golos T., Grayo S., Hannan N., Harris L., Ichizuka K., Illsley N., Iwashita M., Kallol S., Al-Khan A., Lash G., Nagamatsu T., Nakashima A., Niimi K., Nomoto M., Redman C., Saito S., Tanimura K., Tomi M., Usui H., Vatish M., Wolfe B., Yamamoto E., O'Tierney-Ginn P.

    Placenta (Placenta)   2019

    ISSN  01434004

     View Summary

    © 2019 Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2018 there were nine themed workshops, five of which are summarised in this report. These workshops discussed new perspectives and knowledge in the following areas of research: 1) preeclampsia; 2) abnormally invasive placenta; 3) placental infection; 4) gestational trophoblastic disease; 4) drug delivery to treat placental dysfunction.

  • Transport of pregabalin via L-type amino acid transporter 1 (SLC7A5) in human brain capillary endothelial cell line

    Yu Takahashi, Tomohiro Nishimura, Kei Higuchi, Saki Noguchi, Yuma Tega, Toshiki Kurosawa, Yoshiharu Deguchi, Masatoshi Tomi

    Pharmaceutical Research (Pharmaceutical Research)  35 ( 12 ) 246 2018.10

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0724-8741

     View Summary

    © 2018, The Author(s). Purpose: The anti-epileptic drug pregabalin crosses the blood-brain barrier (BBB) in spite of its low lipophilicity. This study was performed to determine whether L-type amino acid transporters (LAT1/SLC7A5 and LAT2/SLC7A8) contribute to the uptake of pregabalin. Methods: Pregabalin uptake by LATs-transfected HEK293 cells or hCMEC/D3 cells, an in vitro human BBB model, was measured by LC-MS/MS analysis. Expression of LAT1 mRNA in hCMEC/D3 cells was determined by quantitative RT-PCR analysis. Results: Overexpression of LAT1, but not LAT2, in HEK293 cells significantly increased the cellular uptake of pregabalin, and the LAT1-mediated uptake was saturable with a Km of 0.288 mM. LAT1-mediated amino acid uptake was inhibited specifically and almost completely in the presence of 1 mM pregabalin. The uptake of pregabalin by hCMEC/D3 cells was sodium-independent, saturable (Km = 0.854 mM), and strongly inhibited by large amino acids at 1 mM, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, a specific system L inhibitor, at 1 mM and by JPH203, a LAT1-selective inhibitor, at 10 μM. Pregabalin uptake in hCMEC/D3 cells was also decreased by 75% by the silencing of LAT1 gene using LAT1 siRNA. Conclusions: Our results indicate that LAT1, but not LAT2, recognizes pregabalin as a substrate. It is suggested that LAT1 mediates pregabalin transport at the BBB.

  • Hypotaurine is a substrate of GABA transporter family members GAT2/Slc6a13 and TAUT/Slc6a6

    Tomohiro Nishimura, Kei Higuchi, Yuko Yoshida, Yuki Sugita-Fujisawa, Kazuaki Kojima, Maiko Sugimoto, Marie Santo, Masatoshi Tomi, Emi Nakashima

    Biological and Pharmaceutical Bulletin (Biological and Pharmaceutical Bulletin)  41 ( 10 ) 1523 - 1529 2018.10

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  09186158

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    © 2018 The Pharmaceutical Society of Japan. Hypotaurine is a precursor of taurine and a physiological antioxidant that circulates in adult and fetal plasma. The purpose of the present study was to clarify whether hypotaurine is a substrate of Slc6a/gammaaminobutyric acid (GABA) transporter family members. Radiolabeled hypotaurine was synthesized from radiolabeled cysteamine and 2-aminoethanethiol dioxygenase. The uptakes of [3H]GABA, [3H]taurine, and [14C]hypotaurine by HEK293 cells expressing mouse GAT1/Slc6a1, TAUT/Slc6a6, GAT3/Slc6a11, BGT1/ Slc6a12, and GAT2/Slc6a13 were measured. TAUT and GAT2 showed strong [14C]hypotaurine uptake activity, while BGT1 showed moderate activity, and GAT1 and GAT3 showed slight but significant activity. Mouse TAUT and GAT2 both showed Michaelis constants of 11 μM for hypotaurine uptake. GAT2-expressing cells pretreated with hypotaurine showed resistance to H2O2-induced oxidative stress. These results suggest that under physiological conditions, TAUT and GAT2 would be major contributors to hypotaurine transfer across the plasma membrane, and that uptake of hypotaurine via GAT2 contributes to the cellular resistance to oxidative stress.

  • Gene expression of A6-like subgroup of ATP-binding cassette transporters in mouse brain parenchyma and microvessels

    Tachikawa Masanori, Toki Hidetoh, Watanabe Masahiko, Masatoshi Tomi, Hosoya Ken ichi, Terasaki Tetsuya

    Anatomical Science International (Anatomical Science International)  93 ( 4 ) 456 - 463 2018.03

    Research paper (scientific journal), Accepted,  ISSN  1447-6959

     View Summary

    © 2018, Japanese Association of Anatomists. The A-subclass of ATP-binding cassette (ABC) transporters is a highly conserved superfamily of potent lipid transporters. Although the ABCA1-like subgroup of ABCA1-4, and A7 have been shown to mediate the transport of endogenous lipids, the roles of the ABCA6-like subgroup transporters, which have been identified as a unique gene cluster on human chromosome 17q24 (ABCA5, A6, A8, A9, and A10) and mouse chromosome 11 (Abca5, a6, a8a, a8b, and a9), remains largely unknown. The purpose of the present study was to clarify the spatial and temporal expression profiles of Abca6-like subgroup transporters in embryonic and postnatal mouse brains by a combination of in situ hybridization and quantitative polymerase chain reaction (PCR) using magnetically isolated brain vascular endothelial cells. In embryonic brains, the transcripts of Abca5, a8a and a8b were detected predominantly in the mantle zone, where postmitotic neurons differentiate. At the postnatal stages, they were expressed in various nuclei and neuronal layers. Abca9 mRNA was detected diffusely in the embryonic and postnatal brains and sequential and/or strong spotted signals were detected in the leptomeninges on the brain surface. PCR detected expression of Abca8a and Abca9 mRNAs in isolated vascular endothelial cells. Expression signals for Abca6 mRNA were hardly observed at any stages examined. These distinct spatio-temporal expression patterns of Abca6-like subgroup transporters may reflect their functional significance and diversity to regulate lipid transport, particularly in neurons, leptomeningeal cells, and vascular endothelial cells.

  • Effect of serotonin transporter genotype on self-reported efficacy and activity changes of brain prefrontal area in response to placebo

    Isawa Minae, Tashiro Ryota, Naruse Chiaki, Yamaguchi Yuki, Itoh Hiroshi, Nishimura Tomohiro, Tomi Masatoshi, Shimada Hideyo, Saito Hidetsugu, Mochizuki Mayumi, Nakashima Emi

    Pharmazie (Pharmazie)  73 ( 1 ) 35 - 41 2018.01

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0031-7144

     View Summary

    Patients benefit from drug therapy not only through pharmacological mechanisms, but also through non-pharmacological action (placebo effect), which may be mediated in part by the prefrontal area of the brain. We consider that the difference between responders and non-responders to placebo might be related to polymorphisms in the serotonin transporter-linked polymorphic region (5-HTTLPR). To study this idea, we performed a randomized double-blind clinical trial using caffeine and lactose (placebo). Activity in the prefrontal area of the brain was measured in terms of blood flow by means of near-infrared spectroscopy (NIRS) as an objective indicator. Self-reported feelings of drowsiness on established scales were used as subjective indicators. Twenty-one subjects in block A took caffeine on the first day and placebo on the third day, and 21 in block B took placebo on the first day and placebo on the third day. After placebo administration, improvement of sleepiness was significantly enhanced, a similar extent to that after caffeine medication. Among the 42 subjects, 22 showed S/S type polymorphism in the serotonin transporter (52.4 %), 17 showed S/L type (40.5 %) and 3 showed L/L type (7.10 %). Statistical analysis of the results indicate that subjects with L/L genotype showed a significantly greater placebo response in terms of both self-reported feeling of drowsiness and blood flow in the prefrontal area of the brain associated with working memory (46 area). Our results indicate that the L/L genotype of 5-HTTLPR, which is rare in Japanese (3.2 %) but common in Americans (32.2 %), may be associated with a greater placebo effect.

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Papers, etc., Registered in KOARA 【 Display / hide

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Reviews, Commentaries, etc. 【 Display / hide

  • 胎児移行性の低い薬物について教えてください

    登美 斉俊

    月刊薬事 (じほう)  58 ( 4 ) 666 - 669 2016.03

    Introduction and explanation (scientific journal), Single Work

  • 紹介 慶應義塾大学薬学部国際交流セミナーWilliam N. Charman先生講演会

    登美 斉俊

    薬剤学 75 ( 6 ) 381 - 382 2015.11

    Meeting report etc., Single Work

  • 紹介 第29回日本薬物動態学会・第19回国際薬物動態学会北米年会合同年会

    登美 斉俊

    薬剤学 75 ( 2 ) 133 - 134 2015.03

    Meeting report etc., Single Work

  • トランスポーターによる胎盤関門透過制御機構の解明

    登美 斉俊

    Drug Delivery System (日本DDS学会)  28 ( 4 ) 364 - 365 2013.09

    Introduction and explanation (scientific journal), Single Work

  • How the brain acts: Factor analysis of placebo effects

    井澤 美苗, 信野 明美, 西村 友宏, 登美 斉俊, 中島 恵美

    日本香粧品学会誌 37 ( 3 ) 197 - 200 2013.09

    Summary of the papers read (national conference and other science council), Joint Work

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Presentations 【 Display / hide

  • マウス胎盤細胞膜MDR1およびBCRPタンパクの妊娠進行に伴う発現量推移

    植田 有美、西村 友宏、野口 幸希、明石 知也、立川 正憲、内田 康雄、寺崎 哲也、登美 斉俊

    第3回トランスポーター研究会関東部会 (千葉) , 2018.11

  • ヒト絨毛癌由来JEG-3細胞の分化過程におけるmiR-126発現がLIN28A発現に与える影響

    潘晓乐、野口幸希、安藤美鈴、竹村 千尋、西村友宏、登美斉俊

    第3回トランスポーター研究会関東部会 (千葉) , 2018.11

  • Lower fetal toxicity and transfer of irbesartan compared to olmesartan in rats

    Ishikawa Y, Nishimura T, Noguchi S, Tomi M

    International Meeting on 22nd Microsomes and Drug Oxidations (MDO) and 33rd Japanese Society for the Study of Xenobiotics (JSSX) (Kanazawa, Japan) , 2018.10

  • Mother-to-fetal transfer of HMG-CoA reductase inhibitors in pregnant rats

    Nishimura T, Yonemura N, Noguchi S, Tomi M

    International Meeting on 22nd Microsomes and Drug Oxidations (MDO) and 33rd Japanese Society for the Study of Xenobiotics (JSSX) (Kanazawa, Japan) , 2018.10

  • Human organic anion transporter 4-mediated transport of angiotensin II receptor blockers

    Noguchi S, Atsuta H, Tobita M, Kimura R, Fukumoto A, Nishimura T, Tomi M

    International Meeting on 22nd Microsomes and Drug Oxidations (MDO) and 33rd Japanese Society for the Study of Xenobiotics (JSSX) (Kanazawa, Japan) , 2018.10

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • トリプトファンバランスに着目した食事による胎児成長支援戦略の構築

    2018.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 登美 斉俊, Grant-in-Aid for Scientific Research (B), Principal Investigator

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

    2015.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 登美 斉俊, Grant-in-Aid for Challenging Exploratory Research, Principal Investigator

     View Summary

    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.

  • Food guide for pregnant women based on placental permeability of ingredients

    2014.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 登美 斉俊, Grant-in-Aid for Scientific Research (B), Principal Investigator

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    We have clarified the protein expression level of nutrient transporters at the brush-border membrane of the human placental barrier formed by single syncytiotrophoblast layer. We have also clarified the protein expression in rat placental barrier formed by double syncytiotrophoblast layers, for estimating placental permeability of transporter substrates across the rat placenta. The higher placental permeability of transporter substrates was observed, however, the estimated permeability was not highly consistent with the measured permeability. There have been thought that two syncytiotrophoblast layers in rodents act functionally as a single layer, but this appears not to be true since we found that MDR1 and BCRP transporters are localized in the second syncytiotrophoblast layer. We need to consider the presence of transporters in the second syncytiotrophoblast layer for estimating placental permeability.

Awards 【 Display / hide

  • 日本薬剤学会奨励賞

    2015.05, The Academy of Pharmaceutical Science and Technology, Japan, 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

  • “2014 Top Reviewer” for Journal of Pharmaceutical Sciences

    2014.12, American Pharmacists Association

 

Courses Taught 【 Display / hide

  • STUDY OF MAJOR FIELD: (PHARMACEUTICS)

    2019

  • SEMINAR: (PHARMACEUTICS)

    2019

  • RESEARCH FOR BACHELOR'S THESIS C

    2019

  • RESEARCH FOR BACHELOR'S THESIS A

    2019

  • PRECLINICAL PRACTICE (1)

    2019

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