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2011 Fiscal Year Final Research Report

Integrated research of histamine system from molecular to wholeanimals and humans using leading-edge technologies

Research Project

  • PDF
Project/Area Number 21390171
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionTohoku University

Principal Investigator

YANAI Kazuhiko  東北大学, 大学院・医学系研究科, 教授 (50192787)

Co-Investigator(Kenkyū-buntansha) WATANABE Takehiko  東北大学, 大学院・医学系研究科, 名誉教授 (70028356)
YOSHIKAWA Takeo  東北大学, 大学院・医学系研究科, 助教 (70506633)
KURAMASU Atsuo  山口大学, 大学院・医学系研究科, 准教授 (90302091)
SAKURAI Eiko  いわき明星大学, 薬学部, 教授 (90153949)
Co-Investigator(Renkei-kenkyūsha) OKAMURA Nobuyuki  東北大学, 大学院・医学系研究科, 准教授 (40361076)
Project Period (FY) 2009 – 2011
Keywordsヒスタミン / 神経変性疾患 / H3受容体 / 分子イメージング / PET / PMAT / H1受容体占拠率 / 膵ランゲルハンス島β細胞
Research Abstract

Using leading-edge te chnologies, this study examined new roles of neuronal histamine which have not been fully dissolved. This study was performed on the experiments of molecular and cellular levels and whole animals, and we attempted the results were directly connected to tra nslational human PET studies. Main findings of this study are as follows : 1)The role of C-terminal on H3 receptors-mediated signal transduction were clarified ; 2)The transport of histamine in the CNS was mediated through a newly-identified non-specific t ransporter, PMAT (plasma membrane monoamine transporter)in astrocytes. 3)The existence and roles of H3 receptors in pancreatic islet cells were discovered for the first time. 4)The roles of histamine receptors on whole animals' behavioral levels were ex amined using histamine receptors knockout mice. 5)Brain pharmacokinetics of antihistamines was revealed using molecular PET imaging on the term of H1 receptor occupancy.

  • Research Products

    (58 results)

All 2012 2011 2010 2009 Other

All Journal Article (27 results) (of which Peer Reviewed: 17 results) Presentation (27 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Safety considerations in the management of allergic diseases : focus on antihistamines2012

    • Author(s)
      Yanai K, Rogala B, Chugh K, Paraskakis E, Pampura AN, Boev R
    • Journal Title

      Current Medical Research & Opinion

      Volume: Vol.28 (4) Pages: 1. 20

    • Peer Reviewed
  • [Journal Article] Anticholinergic activity of antihistamines2012

    • Author(s)
      Yanai K
    • Journal Title

      Clin Neurophysiol

      Volume: 123(4) Pages: 633-4

    • Peer Reviewed
  • [Journal Article] Roles of histamine in exercise-induced fatigue : favouring endurance and protecting against exhaustion2012

    • Author(s)
      Niijima-Yaoita F, Tsuchiya M, Ohtsu H, Yanai K, Sugawara S, Endo Y, Tadano T
    • Journal Title

      Biol Pharm Bull

      Volume: 35(1) Pages: 91-7

    • Peer Reviewed
  • [Journal Article] Positron emission tomography evaluation of sedative properties of antihistamines2011

    • Author(s)
      Yanai K, Zhang D, Tashiro M, Yoshikawa T, Naganuma F, Harada R, Nakamura T, Shibuya K, Okamura N
    • Journal Title

      Expert Opinion on Drug Safety

      Volume: 10(4) Pages: 613

    • Peer Reviewed
  • [Journal Article] The hydrophobic amino acids in putative helix 8 in carboxy-terminus of histamine H3 receptor are involved in receptor-G-protein coupling2011

    • Author(s)
      Kuramasu A, Sukegawa J, Sato T, Sakurai E, Watanabe T, Yanagisawa T, Yanai K
    • Journal Title

      Cell Signal

      Volume: 23(11) Pages: 1843

    • Peer Reviewed
  • [Journal Article] Interaction of histamine and calcitonin gene-related peptide in the formalininduced pain perception in rats2011

    • Author(s)
      Mobarakeh JI, Torkaman-Boutorabi A, Rahimi AA, Ghasri S, Nezhad RM, Hamzely A, Khoshkholgh Sima B, Takahashi K, Nunoki K, Yanai K
    • Journal Title

      Biomed Res

      Volume: 32(3) Pages: 195

    • Peer Reviewed
  • [Journal Article] Brain histamine H1 receptor occupancy of loratadine measured by PET : Comparison of H1 receptor occupancy and proportional impairment ratio2011

    • Author(s)
      Kubo N, Senda M, Ohsumi Y, Sakamoto S, Matsumoto K, Tashiro M, Okamura N, Yanai K
    • Journal Title

      Hum Psychopharmacol

      Volume: 26(2) Pages: 133-139

    • Peer Reviewed
  • [Journal Article] 第二世代抗ヒスタミン薬の薬理学的特徴2011

    • Author(s)
      谷内一彦、長沼史登
    • Journal Title

      日本医事新報

      Volume: 4547 Pages: 57-59

  • [Journal Article] ヒスタミン受容体を理解する2011

    • Author(s)
      谷内一彦、長沼史登、中村正帆、吉川雄朗
    • Journal Title

      DermatologyToday

      Volume: 4 Pages: 4-9

  • [Journal Article] Roles of hypothalamic subgroup histamine and orexin neurons on behavioral responses to sleep deprivation induced by the treadmill method in adolescent rats2011

    • Author(s)
      Xu A, Sakurai E, Kuramasu A, Zhang J, Li J, Okamura N, Zhang D, Yoshikawa T, Watanabe T, Yanai K
    • Journal Title

      J. Pharmacol. Sci

      Volume: 114(4) Pages: 444

    • Peer Reviewed
  • [Journal Article] Next-day Residual Sedative Effect after Nighttime Administration of an OTC Antihistamine Sleepaid, Diphenhydramine, Measured by Positron Emission Tomography2011

    • Author(s)
      Zhang D, Tashiro M, Shibuya K, Okamura N, Funaki Y, Yoshikawa T, Kato M, Yanai K
    • Journal Title

      J. Clin. Psychopharmacol

      Volume: 30(6) Pages: 694-701

    • Peer Reviewed
  • [Journal Article] Effects of a chicken extract on food-deprived activity stress in rats2011

    • Author(s)
      Lu YQ, He RR, Watanabe H, Abe K, Sakurai E, Yanai K, Kurihara H
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 74(6) Pages: 1276

    • Peer Reviewed
  • [Journal Article] Alpha-fluoromethylhistidine, a histamine synthesis inhibitor, inhibits orexin-induced wakefulness in rats2011

    • Author(s)
      Seki Y, Akanmu MA, Matsuura M, Yanai K, Honda K
    • Journal Title

      Behav. Brain Res

      Volume: 207 Pages: 151-154

  • [Journal Article] 脳機能を標的とした新しい痒み治療戦略:痒みイメージング研究の視点から2010

    • Author(s)
      中村正帆、吉川雄朗、谷内一彦
    • Journal Title

      特集「脳とアレルギー」アレルギー・免疫

      Volume: 17(10) Pages: 1868

  • [Journal Article] CONGAコンセンサスに準じたレボセチリジンの評価2010

    • Author(s)
      谷内一彦
    • Journal Title

      特集「新規抗ヒスタミン薬レボセチリジン」医薬ジャーナル

      Volume: 46(10) Pages: 2506-2511

  • [Journal Article] 抗ヒスタミン薬の選択2010

    • Author(s)
      片山一郎、谷内一彦、Christpher Alford、Erwin Gelfand、Ian Hindmarch、幸野健、大久保公裕、Torsten Zuberbier
    • Journal Title

      最適な治療の視点からアレルギー・免疫

      Volume: 17 Pages: 456-468

  • [Journal Article] Methamphetamine-and 3, 4-Methylenedioxymethamphetamine-Induced Behavioral Changes in Histamine H(3)-Receptor Knockout Mice2009

    • Author(s)
      Okuda T, Zhang D, Shao H, Okamura N, Takino N, Iwamura T, Sakurai E, Yoshikawa T, Yanai K
    • Journal Title

      J Pharmacol Sci

      Volume: 111(2) Pages: 167-74

    • Peer Reviewed
  • [Journal Article] Dose dependency of brain histamine H(1)receptor occupancy following oral administration of cetirizine hydrochloride measured using PET with [11C] doxepin2009

    • Author(s)
      Tashiro M, Kato M, Miyake M, Watanuki S, Funaki Y, Ishikawa Y, Iwata R, Yanai K
    • Journal Title

      Hum Psychopharmacol

      Volume: 24(7) Pages: 540-8

    • Peer Reviewed
  • [Journal Article] Roles of the histaminergic neurotransmission on methamphetamine-induced locomotor sensitization and reward : a study of receptors gene knockout mice2009

    • Author(s)
      Takino N, Sakurai E, Kuramasu A, Okamura N, Yanai K
    • Journal Title

      Int Rev Neurobiol

      Volume: 85 Pages: 109-16

    • Peer Reviewed
  • [Journal Article] Enhanced morphine-induced antinociception in histamine H3 receptor gene knockout mice2009

    • Author(s)
      Mobarakeh JI, Takahashi K, Yanai K
    • Journal Title

      Neuropharmacology

      Volume: 57(4) Pages: 409-14

    • Peer Reviewed
  • [Journal Article] Histamine responses of large neostriatal interneurons in histamine H1 and H2 receptor knock-out mice2009

    • Author(s)
      Ogawa S, Yanai K, Watanabe T, Wang ZM, Akaike H, Ito Y, Akaike N
    • Journal Title

      Brain Res Bull

      Volume: 78(4-5) Pages: 189-94

    • Peer Reviewed
  • [Journal Article] Decreased CSF histamine in narcolepsy with and without low CSF hypocretin-1 in comparison to healthy controls2009

    • Author(s)
      Nishino S, Sakurai E, Nevsimalova S, Yoshida Y, Watanabe T, Yanai K, Mignot E
    • Journal Title

      Sleep

      Volume: 32(2) Pages: 175-80

    • Peer Reviewed
  • [Journal Article] ncreased Brain Histamine H1 Receptor Binding in Patients with Anorexia Nervosa2009

    • Author(s)
      Yoshizawa M, Tashiro M, Fukudo S, Yanai K, Utsumi A, Kano M, Karahasi M, Endo Y, Morisita J, Sato Y, Adachi M, Itoh M, Hongo M
    • Journal Title

      Biol Psychiatry

      Volume: 65(4) Pages: 329-35

    • Peer Reviewed
  • [Journal Article] ヒスタミンH1、H2受容体遺伝子欠損マウスの作成と意義2009

    • Author(s)
      谷内一彦、赤池紀生
    • Journal Title

      生体の科学

      Volume: 60(5) Pages: 442-443

  • [Journal Article] 抗ヒスタミン薬と認知機能:dimebonはアルツハイマー病の認知機能を改善する最近の話題2009

    • Author(s)
      谷内一彦、吉川雄朗
    • Journal Title

      日薬理誌

      Volume: 134 Pages: 235

  • [Journal Article] 抗ヒスタミン薬による運転能力障害に対する認識鼻アレルギーフロンティア2009

    • Author(s)
      谷内一彦、田代学、千葉真
    • Volume
      9(1)
    • Pages
      58-64
  • [Journal Article] 抗ヒスタミン薬の新分類2009

    • Author(s)
      熊谷雄治、Ian Hindmarch、谷内一彦
    • Journal Title

      Not Impairing antihistamine (NIaH)とImpairing antihistamine (IaH)診断と治療

      Volume: 97(1) Pages: 77-186

  • [Presentation] Potential Central Sedative Effects of Antihistamine Eye-drops : Histamine H1 Receptor Occupancy by PET2012

    • Author(s)
      Dongying Zhang, Manabu Tashiro, Nobuyuki Okamura, and Kazuhiko Yanai
    • Organizer
      第32回日本臨床薬理学会
    • Place of Presentation
      浜松
    • Year and Date
      20121201-03
  • [Presentation] 受容体遮断は睡眠除去した野生型とH1受容体遺伝子ノックアウトマウスで自発運動量を増加させる2012

    • Author(s)
      アタイエフモーセン、長沼史登、渋谷勝彦、中村正帆、吉川雄朗、岡村信行、谷内一彦
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Year and Date
      20120314-16
  • [Presentation] アルツハイマー病の病理画像化を目指したF-18標識PETプローブの開発2012

    • Author(s)
      古本祥三、岡村信行、樋口真人、岩田錬、工藤幸司、谷内一彦
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Year and Date
      20120314-16
  • [Presentation] 小動物用PET/CTを用いた抗ヒスタミン薬レボセチリジンの鎮静性評価2012

    • Author(s)
      飯田智光、古本祥三、船木善仁、石渡喜一、長沼史登、原田龍一、岩田錬、谷内一彦
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Year and Date
      20120314-16
  • [Presentation] ヒスタミンH4受容体を介するケモタキシスにおける低分子量Gタンパク質Racの関与2012

    • Author(s)
      倉増敦朗、若林深恵、乾誠、谷内一彦
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Year and Date
      20120314-16
  • [Presentation] ヒトアストロサイト-マ由来細胞株はPMATを介してドパミンを取り込む2012

    • Author(s)
      長沼史登、吉川雄朗、中村正帆、飯田智光、谷内一彦
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Year and Date
      20120314-16
  • [Presentation] アルツハイマー病患者における脳内アセチルコリンエステラーゼへの[11C] ドネぺジル結合量と塩酸ドネぺジル治療反応性との関連性2012

    • Author(s)
      岡村信行、糟谷昌志、石川博康、田中尚文、船木善仁、岩田錬、目黒謙一、谷内一彦
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Year and Date
      20120314-16
  • [Presentation] 正常ヒトアストロサイトによるヒスタミン取り込みはPMATを介して行われる2012

    • Author(s)
      吉川雄朗、長沼史登、中村正帆、飯田智光、谷内一彦
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Year and Date
      20120314-16
  • [Presentation] [18F] THK-523によるin vivoタウイメージング2012

    • Author(s)
      原田龍一、岡村信行、古本祥三、吉川雄朗、荒井啓行、谷内一彦、工藤幸司
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Year and Date
      20120314-16
  • [Presentation] ヒスタミンH3受容体による膵β細胞機能の制御2012

    • Author(s)
      中村正帆、吉川雄朗、野口直哉、長沼史登、原田龍一、アタイエフモーセン、飯田智光、笠島敦子、笹野公伸、谷内一彦
    • Organizer
      第85回日本薬理学会
    • Place of Presentation
      京都
    • Year and Date
      20120314-16
  • [Presentation] H3 receptor blockade increases locomotor activity in mice2012

    • Author(s)
      Attayeb Mohsen, Fumito Naganuma, Tadaho Nakamura, Katsuhiko Shibuya, Takeo Yoshikawa, Kazuhiku Yanai
    • Organizer
      JSPS-NRF Asian Science Seminar
    • Place of Presentation
      ソウル韓国
    • Year and Date
      20120213-17
  • [Presentation] The Distribution Change of Trace Metal in Methamphetamine Treated Mice Brain Slices by In-Air Micro-PIXE JSPS-NRF Asian Science Seminar2012

    • Author(s)
      Eiko Sakurai, Keizo Ishii, Takahiro Satoh, Tomohiro Kamiya, Nobuyuki Okamura, Kazuhiko Yanai
    • Place of Presentation
      ソウル韓国
    • Year and Date
      20120213-17
  • [Presentation] Histamine H1 receptor occupancy of new generation antidepressant : in vivo positron emission tomography study2012

    • Author(s)
      Hirotoshi Sato, Chihiro Ito, Manabu Tashiro, Katsuhiko Shibuya, Zhang Dongying, Kotaro Hiraoka, Yoshihito Funaki, Ren Iwata, Hiroo Matsuoka and Kazuhiko Yanai
    • Organizer
      JSPS-NRF Asian Science Seminar
    • Place of Presentation
      ソウル韓国
    • Year and Date
      20120213-17
  • [Presentation] Interaction of histamine and calcitonin gene-related peptide in the formalin-induced pain perception in rats2012

    • Author(s)
      Jalal Izadi Mobarakeh, Kazuhiro Takahashi, Kazuo Nunoki and Kazuhiko Yanai
    • Organizer
      JSPS-NRF Asian Science Seminar
    • Place of Presentation
      ソウル韓国
    • Year and Date
      20120213-17
  • [Presentation] Cholinergic deficit and response to donepezil therapy in Parkinson's disease with dementia2012

    • Author(s)
      Kotaro Hiraoka, Nobuyuki Okamura, Yoshihito Funaki, Akiko Hayashi, Manabu Tashiro, Kinya Hisanaga, Toshikatsu Fujii, Atsushi Takeda, Kazuhiko Yanai, Ren Iwata, and Etsuro Mori
    • Organizer
      SPS-NRF Asian Science Seminar
    • Place of Presentation
      ソウル韓国
    • Year and Date
      20120213-17
  • [Presentation] Wavelength-dependent detection of senile plaques and neurofibrillary tangles with novel fluorescent probes2012

    • Author(s)
      Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Takeo Yoshikawa, Yukitsuka Kudo, Kazuhiko Yanai
    • Organizer
      JSPS-NRF Asian Science Seminar
    • Place of Presentation
      ソウル韓国
    • Year and Date
      20120213-17
  • [Presentation] Histamine H3 Receptor Regulates the Functions of Pancreatic β-cell2012

    • Author(s)
      adaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Ryuichi Harada, Attayeb Mohsen, Masashi Saito, and Kazuhiko Yanai
    • Organizer
      JSPS-NRF Asian Science Seminar
    • Place of Presentation
      ソウル韓国
    • Year and Date
      20120213-17
  • [Presentation] Molecular PET Imaging of Histamine H1 Receptors in Humans : Recent Progress2011

    • Author(s)
      Fumito Naganuma, Kazuhiko Yanai, and Manabu Tashiro
    • Organizer
      Anxiety and Depression, SFN2011
    • Place of Presentation
      DC米国
    • Year and Date
      20111110-11
  • [Presentation] PETによる新規抗うつ薬(NaSSA・SSRI)のヒト脳内H1受容体占拠率の解析2011

    • Author(s)
      佐藤博俊、伊藤千裕、田代学、渋谷勝彦、張冬頴、平岡宏太良、船木善仁、岩田錬、谷内一彦、松岡洋夫
    • Organizer
      第41回日本神経精神薬理学会
    • Place of Presentation
      東京
    • Year and Date
      20111027-29
  • [Presentation] Locomotor activity and anxiolytic-like behaviors are increased by histamine H3 receptor antagonists2011

    • Author(s)
      ttayef Mohsen, Fumito Naganuma, Tadaho Nakamura, Katsuhiko Shibuya, Takeo Yoshikawa, Nobuyuki Okamura, and Kazuhiko Yanai
    • Organizer
      第15回日本ヒスタミン学会
    • Place of Presentation
      盛岡
    • Year and Date
      20111021-22
  • [Presentation] インスリン分泌膵β細胞におけるヒスタミン3型受容体の発現と機能2011

    • Author(s)
      中村正帆、吉川雄朗、野口直哉、大杉真也、笠島敦子、笹野公伸、谷内一彦
    • Organizer
      第15回日本ヒスタミン学会
    • Place of Presentation
      盛岡
    • Year and Date
      20111021-22
  • [Presentation] 正常ヒトアストロサイトによるヒスタミン取り込み機構の解明2011

    • Author(s)
      長沼史登、吉川雄朗、中村正帆、井筒敏恵、谷内一彦
    • Organizer
      第15回日本ヒスタミン学会
    • Place of Presentation
      盛岡
    • Year and Date
      20111021-22
  • [Presentation] ヒスタミン研究の最近の進歩2011

    • Author(s)
      谷内一彦
    • Organizer
      第15回日本ヒスタミン学会
    • Place of Presentation
      盛岡
    • Year and Date
      20111021-22
  • [Presentation] Histamine H3 receptors antagonists increase anxiogenic-like behaviors and locomotor activity2011

    • Author(s)
      Attayef Mohsen, Fumito Naganuma, Tadaho Nakamura, Katsuhiko Shibuya, Takeo Yoshikawa, Nobuyuki Okamura, and Kazuhiko Yanai
    • Organizer
      第62回日本薬理学会北部会
    • Place of Presentation
      仙台
    • Year and Date
      20110929-30
  • [Presentation] 膵β細胞におけるヒスタミン3型受容体の発現とインスリン分泌での役割2011

    • Author(s)
      中村正帆、大杉真也、吉川雄朗、谷内一彦
    • Organizer
      第62回日本薬理学会北部会
    • Place of Presentation
      仙台
    • Year and Date
      20110929-30
  • [Presentation] ヒトアストロサイトによるヒスタミン取り込み機構2011

    • Author(s)
      長沼史登、吉川雄朗、中村正帆、井筒敏恵、谷内一彦
    • Organizer
      第62回日本薬理学会北部会
    • Place of Presentation
      仙台
    • Year and Date
      20110929-30
  • [Presentation] ヒトアストロサイトによるヒスタミン取り込み機構について2011

    • Author(s)
      長沼史登、吉川雄朗、中村正帆、井筒敏恵、谷内一彦
    • Organizer
      第54回日本神経化学大会
    • Place of Presentation
      仙台
    • Year and Date
      20110925-28
  • [Book] ヒスタミンの作用、選択的H1受容体拮抗作用宮地良樹、ファーマーナビゲーター2012

    • Author(s)
      谷内一彦
    • Total Pages
      42-55
    • Publisher
      メディカルレビュー社
  • [Book] 特集「ヒスタミンH1受容体拮抗薬の臨床」アレルギーの臨床2010

    • Author(s)
      谷内一彦
    • Total Pages
      1236
    • Publisher
      北隆館
  • [Remarks]

    • URL

      http://www.miec.umin.mech.cgi-bin/gaiyo.cgi

  • [Remarks]

    • URL

      http://www.pharmacology.med.tohoku.ac.jp/

URL: 

Published: 2013-07-31  

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