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Mechanisms modulating pregnenolone sulfotransferase expression and effects of anesthetic agents in rat C6 glial cells

Research Project

Project/Area Number 18390539
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionKagoshima University

Principal Investigator

KOHJITANI Atsushi  Kagoshima University, 大学院・医歯学総合研究科, 准教授 (60304325)

Co-Investigator(Kenkyū-buntansha) 花崎 元彦  岡山大学, 大学院・医歯薬学総合研究科, 助教 (60379790)
宮脇 卓也  岡山大学, 大学院・医歯薬学総合研究科, 教授 (00219825)
屋島 浩記  鹿児島大学, 医学部・歯学部附属病院, 助教 (20381155)
Co-Investigator(Renkei-kenkyūsha) HANAZAKI Motohiko  岡山大学, 大学院・医歯薬学総合研究科, 助教 (60379790)
MIYAWAKI Takuya  岡山大学, 大学院・医歯薬学総合研究科, 教授 (00219825)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥8,400,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥600,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥5,800,000 (Direct Cost: ¥5,800,000)
Keywordsスルフォトランスフェラーゼ / ニューロステロイド / 学習・記憶 / NMDA 受容体 / 麻酔薬 / 全身麻酔 / 一酸化窒素 / グリア細胞 / NMDA受容体
Research Abstract

硫酸プレグネノロンは中枢神経系において学習・記憶に重要な役割を果たすニューロステロイドである.中枢神経系の支持組織であるグリア細胞において、硫酸プレグネノロンの産生を触媒する酵素スルフォトランスフェラーゼ(SULT)の発現調節機構を検討した.ラットC6グリア細胞株を種々の興奮性アミノ酸受容体サブタイプの作動薬およびNO産生刺激条件に暴露し、SULT2B1aアイソフォームmRNA発現をリアルタイムPCR法で測定した.培養液中のnitrite濃度をGriess Reactionによって測定し、NO産生量とした.グルタミン酸およびAMPAは、受容体の脱感作を予防するcyclothiazideの存在下で用量依存的にSULT2B1a発現を抑制した.グルタミン酸によるSULT2B1a発現の抑制は、AMPA受容体拮抗薬NBQX、神経型NO合成酵素(nNOS)阻害薬7-NIの前処置により回復した.LPS/TNF-によるサイトカイン反応でC6グリア細胞に誘導型NO合成酵素(iNOS)を誘導するとSULT2B1a発現は抑制され、この抑制はiNOS阻害薬L-NILで部分的に回復した.外因性NOドナーは用量依存的にSULT2B1a発現を抑制した.グルタミン酸、外因性NOドナー、iNOS誘導はいずれもnitrite産生量を増加させた. C6グリア細胞を静脈麻酔薬ミダゾラムに暴露すると、SULT2B1a発現は抑制された.以上より、C6グリア細胞におけるSULT2B1a発現は興奮性アミノ酸受容体のAMPA型サブタイプを介するNOの細胞内シグナル伝達経路により調節されること、ミダゾラムは臨床使用濃度の短時間暴露でSULT2B1a発現を抑制することが明らかになった.

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (37 results)

All 2009 2008 2007 2006

All Journal Article (22 results) (of which Peer Reviewed: 15 results) Presentation (15 results)

  • [Journal Article] Regulation of SULT2B1a (pregnenolone sulfotransferase) expression in rat C6 glioma cells : relevance of AMPA receptor-mediated NO signaling2008

    • Author(s)
      Kohjitani A, Fuda H, Hanyu O, Strott CA
    • Journal Title

      Neuroscience Letters 430

      Pages: 75-80

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Y-27632 augments the isoflurane-induced relaxation of bronchial smooth muscle in rats2008

    • Author(s)
      Hanazaki M, Chiba Y, Yokoyama M, Morita K, Kohjitani A, Sakai H, Misawa M
    • Journal Title

      Journal of Smooth Muscle Research 44(6)

      Pages: 189-193

    • NAID

      130000860913

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dexmedetomidine potentiates local anesthetic action of lidocaine via an alpha-2A adrenoceptor2008

    • Author(s)
      Yoshitomi T, Kohjitani A, Shimada M, Miyawaki T
    • Journal Title

      Anesthesia & Analgesia 107

      Pages: 96-101

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rho-kinase (ROCK) inhibitors augment the inhibitory effect of propofol on rat bronchial smooth muscle contraction2008

    • Author(s)
      Hanazaki M, Yokoyama M, Morita K, Kohjitani A, Sakai H, Chiba Y, Misawa M
    • Journal Title

      Anesthesia & Analgesia 106

      Pages: 1765-1771

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Accumulated oropharyngeal water increases coughing during dental treatment with intravenous sedation2008

    • Author(s)
      Kohjitani A, Egusa M, Shimada M, Miyawaki T
    • Journal Title

      Journal of Oral Rehabilitation 35

      Pages: 203-208

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oral midazolam for sedation in minor oral operations in children : a retrospective study2008

    • Author(s)
      Kohjitani A, Higuchi H, Shimada M, Miyawaki T
    • Journal Title

      British Journal of Oral and Maxillofacial Surgery 46

      Pages: 330-331

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rho-kinase inhibitors augment the inhibitory effect of propofol on rat bronchial smooth muscle contraction.2008

    • Author(s)
      Hanazaki M, Yokoyama M, Morita K, Kohiitani A, Sakai H, Chiba Y, Misawa M.
    • Journal Title

      Anesthesia & Analgesia 106

      Pages: 1765-1771

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dexmedetomidine enhances the local anesthetic action of lidocaine via an alpha-2 adrenoceptor.2008

    • Author(s)
      Yoshitomi T, Kohjitani A, Maeda S, Higuchi H, Shimada M, Miyawaki T.
    • Journal Title

      Anesthesia & Analgesia 107

      Pages: 96-101

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Y-27632 augments the isoflurane-induced relaxation of bronchialsmooth muscle in rats.2008

    • Author(s)
      Hanazaki M, Chiba Y, Yokoyama M, Morita K, Kohjitani A, Sakai H, Misawa M.
    • Journal Title

      Journal of Smooth Muscle Research 44

      Pages: 189-193

    • NAID

      130000860913

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of SULT2Bla (pregnenolone sulfotransferase) expression in rat C6 glioma cells: relevance of AMPA receptor-mediated NO signaling.2008

    • Author(s)
      Kohjitani A, Fuda H, Hanyu O, Strott CA.
    • Journal Title

      Neuroscience Letters 430

      Pages: 75-80

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accumulated oropharyngeal water increases coughing during dental treatment with intravenous sedation2008

    • Author(s)
      Kohjitani A, Shimada M, Miyawaki T.
    • Journal Title

      Journal of Oral Rehabilitation 35

      Pages: 203-208

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oral midazolam for sedation in minor oral operations in children: a retrospective study.2008

    • Author(s)
      Kohjitani A, Higuchi H, Shimada M, Miyawaki T.
    • Journal Title

      British Journal of Oral and Maxillofacial Surgery 46(in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rho-kinase (ROCK) inhibitors augment the inhibitory effect of propofol on rat bronchial smooth muscle contraction.2008

    • Author(s)
      Hanazaki M, Yokoyama M, Morita K, Kohjitani A, Sakai H, Chiba Y, Misawa M.
    • Journal Title

      Anesthesia & Analgesia 106(in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dexmedetomidine potentiates local anesthetic action of lidocaine via an alpha-2A adrenoceptor.2008

    • Author(s)
      Yoshitomi T, Kohjitani A, Shimada M, Miyawaki T.
    • Journal Title

      Anesthesia & Analgesia 107(in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 麻酔薬による一酸化窒素(NO)を介した食道平滑筋弛緩反応の抑制機序2007

    • Author(s)
      糀谷淳
    • Journal Title

      鹿児島大学歯学部紀要 27

      Pages: 1-13

    • NAID

      120001392987

    • Related Report
      2008 Final Research Report
  • [Journal Article] Accumulated oropharyngeal water increases coughing during dental treatment with intravenous sedation.2007

    • Author(s)
      Kohjitani A, Egusa M, Shimada M, Miyawaki T.
    • Journal Title

      Journal of Oral Rehabilitation (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Requirement of oral midazolam for sedation of paediatric patients undergoing minor oral and maxillofacial surgery : a retrospective analysis in relevance to age.2007

    • Author(s)
      Hohjitani A, Higuchi H, Shimada M, Miyawaki T.
    • Journal Title

      British Journal of Oral and Maxillofacial Surgery (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 麻酔薬による一酸化窒素(NO)を介した食道平滑筋弛緩反応の抑制機序2007

    • Author(s)
      粕谷 淳
    • Journal Title

      鹿児島大学歯学部紀要 27(印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cloning, characterization and tissue expression of rat SULT2B1a and SULT2B1b steroid/sterol sulfotransferase isoforms : divergence of the rat SULT2B1 gene structure from orthologous human and mouse genes2006

    • Author(s)
      Kohjitani A, Fuda H, Hanyu O, Strott CA
    • Journal Title

      Gene 367

      Pages: 66-73

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cloning, characterization and tissue expression of rat SULT2Bla and SULT2B1b steroid/sterol sulfotransferase isoforms : divergence of the rat SULT2B1 gene structure from orthlogous human and mouse genes.2006

    • Author(s)
      Kohjitani A, Fuda H, Hanyu O, Strott CA.
    • Journal Title

      Gene 367

      Pages: 66-73

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 知的障害者歯科治療時のミダゾラム・プロポフォールによる静脈内鎮静法に対する抗てんかん薬内服の影響について.2006

    • Author(s)
      西 周子, 吉田啓太, 友安弓子, 樋口仁, 粕谷 淳, 前田 茂, 宮脇卓也, 嶋田昌彦
    • Journal Title

      日本歯科麻酔学会雑誌 34・2

      Pages: 169-172

    • NAID

      10018113921

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 知的障害者歯科治療における精密鎮静法の試み-Bispectral Index(BIS)およびTarget Controlled Infusion(TCI)の応用-2006

    • Author(s)
      樋口 仁, 前田 茂, 粕谷 淳, 吉田啓太, 泰泉寺紋子, 林由起子, 友安弓子, 渡辺禎久, 宮脇卓也
    • Journal Title

      岡山歯学会雑誌 25・2

      Pages: 53-57

    • Related Report
      2006 Annual Research Report
  • [Presentation] Y-27632はイソフルランの気道平滑筋弛緩作用を増強する2009

    • Author(s)
      花崎元彦、千葉義彦、横山正尚、森田潔、糀谷淳、酒井寛泰、三澤美和
    • Organizer
      第82回日本薬理学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-16
    • Related Report
      2008 Final Research Report
  • [Presentation] Effects of sphingosylphosphorylcholine on rat bronchial smooth muscle2008

    • Author(s)
      Hanazaki M, Yokoyama M, Morita K, Kohjitani A, Chiba Y
    • Organizer
      The 2008 Annual Meeting of the American Society of Anesthesiologists
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2008-10-20
    • Related Report
      2008 Final Research Report
  • [Presentation] Effects of sphingosylphosphorylcholine on rat bronchial smooth musclecontraction.2008

    • Author(s)
      Hanazaki M, Yokoyama M, Morita K, Kohjitani A, Chiba Y.
    • Organizer
      The 2008 Annual Meeting of the American Society of Anesthesiologists
    • Place of Presentation
      Orlando, FL, USA
    • Year and Date
      2008-10-20
    • Related Report
      2008 Annual Research Report
  • [Presentation] 気道平滑筋におけるカルシウム感受性調節と麻酔薬2008

    • Author(s)
      花崎元彦、横山正尚、森田 潔、糀谷 淳、千葉義彦、三澤美和
    • Organizer
      第118回日本薬理学会関東部会
    • Place of Presentation
      東京
    • Year and Date
      2008-06-07
    • Related Report
      2008 Final Research Report
  • [Presentation] Dexmedetomidine combined withlidocaine inhibits carrageenin-induced edemaat injection site2007

    • Author(s)
      Miyawaki T, Maeda S, Higuchi H, KohjitaniA, Shimada M
    • Organizer
      The 2007 Annual Meeting of the American Society of Anesthesiologists
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2007-10-14
    • Related Report
      2008 Final Research Report
  • [Presentation] Midazolam attenuates SULT2B1a (pregnenolone sulfotransferase) expression in rat C6 glioma cells2007

    • Author(s)
      Kohjitani A, Okushima K, Miyawaki T, Hanazaki M, Sugiyama K
    • Organizer
      The 2007 Annual Meeting of the American Society of Anesthesiologists
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2007-10-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Effects of PDE3 inhibitors olprinone and milrinone on rat bronchial smooth muscle contraction2007

    • Author(s)
      Hanazaki M, Yokoyama M, Morita K, Kohjitani A, Chiba Y
    • Organizer
      The 2007 Annual Meeting of the American Society of Anesthesiologists
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2007-10-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Effect of furosemide on rat bronchial smooth muscle contraction with acetylcholine2007

    • Author(s)
      Hanazaki M, Yokoyama M, Morita K, Kohjitani A, Chiba Y
    • Organizer
      The 2007 Annual Meeting of the American Society of Anesthesiologists
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2007-10-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Midazolam attenuates SULT2Bla (pregnenolone sulfotransferase) expression in rat C6 glioma cells.2007

    • Author(s)
      Kohjitani A, Okushima K, Miyawaki T, Hanazaki M, Sugiyama K.
    • Organizer
      The 2007 Annual Meeting of the American Society of Anesthesiologists
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2007-10-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] ラットC6グリア細胞株のスルフォトランスフェラーゼ遺伝子発現に及ぼすミダゾラムの影響2007

    • Author(s)
      糀谷淳、屋島浩記、宮脇卓也、椙山加綱
    • Organizer
      第35回日本歯科麻酔学会総会・学術集会
    • Place of Presentation
      北九州
    • Year and Date
      2007-10-05
    • Related Report
      2008 Final Research Report
  • [Presentation] Effects of Rho-kinase inhibitors on anesthetics-induced relaxation of rat bronchial smooth muscle2007

    • Author(s)
      Hanazaki M, Yokoyama M, Morita K, Kohjitani A, Chiba Y, Misawa M
    • Organizer
      International Anesthesia Research Society 81st Clinical & Scientific Congress
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2007-03-24
    • Related Report
      2008 Final Research Report
  • [Presentation] Effects of PDE4 inhibitors rolipram and ICI63197 on rat bronchial smooth muscle contraction2006

    • Author(s)
      Hanazaki M, Kohjitani A, Yokoyama M, Morita K
    • Organizer
      The 2006 Annual Meeting of the American Society of AnesthesiologistsThe 2006 Annual Meeting of the American Society of Anesthesiologists
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2006-10-15
    • Related Report
      2008 Final Research Report
  • [Presentation] Effect of Y-27632 on isoflurane-induced inhibitory effect on rat bronchial smooth muscle contraction2006

    • Author(s)
      Hanazaki M, Kohjitani A, Yokoyama M, Morita K
    • Organizer
      The 2006 Annual Meeting of the American Society of Anesthesiologists
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2006-10-15
    • Related Report
      2008 Final Research Report
  • [Presentation] H-1152 augments the inhibitory effect of propofol on rat bronchial smooth muscle contraction2006

    • Author(s)
      Hanazaki M, Kohjitani A, Yokoyama M, Morita K
    • Organizer
      The 2006 Annual Meeting of the American Society of Anesthesiologists
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2006-10-15
    • Related Report
      2008 Final Research Report
  • [Presentation] 学習・記憶増強酵素スルフォトランスフェラーゼについて2006

    • Author(s)
      糀谷淳
    • Organizer
      第3回日本歯科麻酔学会中国・四国地方会
    • Place of Presentation
      岡山
    • Year and Date
      2006-07-29
    • Related Report
      2008 Final Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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