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2013 Fiscal Year Final Research Report

Pain regulation by PKA and calcineurin through functional modulation of T-type calcium channels

Research Project

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Project/Area Number 23590729
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pain science
Research InstitutionKinki University

Principal Investigator

KAWABATA Atsufumi  近畿大学, 薬学部, 教授 (20177728)

Co-Investigator(Kenkyū-buntansha) SEKIGUCHI Fumiko  近畿大学, 薬学部, 准教授 (90271410)
TSUBOTA Maho  近畿大学, 薬学部, 助教 (90510123)
Project Period (FY) 2011 – 2013
Keywordsカルシウムチャネル / PKA / カルシニューリン / 痛み / 神経突起伸長
Research Abstract

Among three isoforms of T-type calcium channels, Cav3.2 expressed abundantly in the peripheral ending of nociceptors plays a critical role in nociceptive processing. We thus examined molecular mechanisms for functional regulation of Cav3.2 by phosphorylation and dephosphorylation, and its impact on pain signals. Our data show that PKA, activated by stimulation of prostaglandin EP4 receptors in an AKAP150-dependent manner, phosphorylates and functionally upregulates Cav3.2, leading to hyperalgesia, and that calcineurin, a phosphatase, negatively regulates Cav3.2 functions.

  • Research Products

    (19 results)

All 2014 2013 2012 2011 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (15 results) Remarks (1 results)

  • [Journal Article] T-type calcium channels : functional regulation and implication in pain signaling2013

    • Author(s)
      Sekiguchi, F., Kawabata, A
    • Journal Title

      J. Pharmacol. Sci

      Volume: Vol. 122 Pages: 244-250

    • DOI

      10.1254/jphs.13R05CP

    • Peer Reviewed
  • [Journal Article] AKAP-dependent sensitization of Ca_v3.2 channels via the EP_4 receptor/cyclic AMP pathway mediates prostaglandin E_2-induced mechanical hyperalgesia2013

    • Author(s)
      Sekiguchi, F., Aoki, Y., Nakagawa, M., Kanaoka, D., Nishimoto, Y., Tsubota- Matsunami, M., Yamanaka, R., Yoshida, S. and Kawabata, A
    • Journal Title

      Br. J. Pharmacol

      Volume: Vol. 168 Pages: 734-745

    • DOI

      10.1111/j.1476-5381.2012.02174.x

    • Peer Reviewed
  • [Journal Article] Prostaglandin E_2 and pain : an update2011

    • Author(s)
      Kawabata, A
    • Journal Title

      Biol. Pharm. Bull

      Volume: Vol. 34 Pages: 1170-1173

    • DOI

      10.1248/bpb.34.1170

    • Peer Reviewed
  • [Presentation] カルシニューリン阻害薬タクロリムスはカプサイシン誘起結腸痛を増強する2014

    • Author(s)
      寺田侑加, 坪田真帆, 関口富美子, 和田恭一, 桒原健, 髙田充隆, 川畑篤史
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Year and Date
      20140319-21
  • [Presentation] NG108-15細胞におけるdibutyryl cyclic AMP誘起神経分化への内因性硫化水素とCa_v3.2 T型Ca^<2+>チャネルの関与2013

    • Author(s)
      竹田優希, 金岡大樹, 関口富美子, 吉田繁, 川畑篤史
    • Organizer
      生体機能と創薬シンポジウム2013
    • Place of Presentation
      福岡
    • Year and Date
      20130829-30
  • [Presentation] Modulation of Ca_v3.2 T-type calcium channels by endogenous mediators : impact on pain signals and others2013

    • Author(s)
      Kawabata, A
    • Organizer
      3^<rd> International Calcium Channel Conference
    • Place of Presentation
      Krabi, Thailand
    • Year and Date
      20130324-29
  • [Presentation] マウスにおいてprostaglandin E2により誘起されるT型Ca^<2+>チャネルを介する機械的痛覚過敏の特徴:EP2/PKA経路における足場タンパクAKAP150の重要性とEP1/PKC経路の関与について2013

    • Author(s)
      竹中秀, 中村早織, 坪田真帆, 関口富美子, 川畑篤史
    • Organizer
      第124回日本薬理学会近畿部会
    • Place of Presentation
      京都
    • Year and Date
      2013-11-01
  • [Presentation] Molecular mechanisms for the neurite outgrowth caused by prostaglandin E_2 in mouse dorsal root ganglion cells2012

    • Author(s)
      Maeda, T., Mitani, K., Yamagata, R., Sekiguchi, F., Kawabata, A
    • Organizer
      Neuroscience 2012
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      20121013-27
  • [Presentation] Roles of endogenous hydrogen sulfide in the cyclic AMP-induced neuronal differentiation in NG108-15 cells2012

    • Author(s)
      Kanaoka, D., Takeda, Y., Sekiguchi, F., Yoshida, S., Kawabata, A
    • Organizer
      Neuroscience 2012
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      20121013-27
  • [Presentation] マウス脊髄後根神経節培養細胞のプロスタグランジンE_2/cyclic AMP系を介する神経突起伸長におけるT型Ca^<2+>チャネルおよびK^+チャネルの役割2012

    • Author(s)
      山縣亮介, 前田貴史, 三谷健治, 関口富美子, 川畑篤史
    • Organizer
      生体機能と創薬シンポジウム2012
    • Place of Presentation
      神戸
    • Year and Date
      20120830-31
  • [Presentation] NG108-15細胞とラット後根神経節細胞におけるCa_v3.2 T型Ca^<2+>チャネル機能のcyclic AMP依存性増強メカニズムの解析2012

    • Author(s)
      金岡大樹, 山中瑠美, 関口富美子, 吉田繁, 川畑篤史
    • Organizer
      第122回日本薬理学会近畿部会
    • Place of Presentation
      豊中
    • Year and Date
      2012-11-16
  • [Presentation] 知覚神経細胞におけるcyclic AMP誘起神経突起伸長に対するT型Ca^<2+>チャネルおよびK^+チャネルの関与2012

    • Author(s)
      前田貴史, 山縣亮介, 三谷健治, 田中友香里, 関口富美子, 川畑篤史
    • Organizer
      第122回日本薬理学会近畿部会
    • Place of Presentation
      豊中
    • Year and Date
      2012-11-16
  • [Presentation] Prostaglandin E_2-induced sensitization of T-type Ca^<2+> channels : a mechanism for mechanical hyperalgesia2012

    • Author(s)
      Kanaoka, D., Sekiguchi, F., Nakagawa, M., Aoki Y., Nishimoto Y., Yoshida, S., Tsubota-Matsunami, M, Kawabata, A
    • Organizer
      A Satellite Symposium of IUPHAR-GI Section, International Ulcer Week 2012
    • Place of Presentation
      東京
    • Year and Date
      2012-07-12
  • [Presentation] NG108-15細胞のcyclic AMPを介した神経分化への内因性硫化水素の役割2012

    • Author(s)
      金岡大樹, 竹田優希, 関口富美子, 吉田繁, 川畑篤史
    • Organizer
      第121回日本薬理学会近畿部会
    • Place of Presentation
      徳島
    • Year and Date
      2012-06-29
  • [Presentation] マウスにおけるprostaglandin E_<2 >誘起機械的痛覚過敏の発現にはCa_v3.2 T型Ca^<2+>チャネル活性化が関与する~プロテインキナーゼAおよびCの役割~2012

    • Author(s)
      中村早織, 坪田真帆, 川畑篤史
    • Organizer
      第121回日本薬理学会近畿部会
    • Place of Presentation
      徳島
    • Year and Date
      2012-06-29
  • [Presentation] AKAP-dependent modulation of phosphorylation levels of Ca_v3.2 T-type calcium channels by protein kinase A and calcineurin : implications for mechanical pain sensitivity2011

    • Author(s)
      Sekiguchi, F., Kanaoka, D., Nakagawa, M., Aoki, Y., Nishimoto, Y., Yoshida, S., Matsunami, M., Kawabata, A
    • Organizer
      Neuroscience 2011
    • Place of Presentation
      Washington, DC
    • Year and Date
      20111112-16
  • [Presentation] Sensitization of T-type calcium channels by prostaglandin E_2 via the EP4 receptor/cyclic AMP/protein kinase A pathway : a possible mechanism for mechanical hyperalgesia2011

    • Author(s)
      Kanaoka, D., Sekiguchi, F., Nakagawa, M., Aoki, Y., Nishimoto, Y., Yoshida, S., Matsunami, M., Kawabata, A
    • Organizer
      Neuroscience 2011
    • Place of Presentation
      Washington, DC
    • Year and Date
      20111112-16
  • [Presentation] PGE_2誘起機械的痛覚過敏にはEP4受容体/PKA系によるCa_v3.2 T型Ca^<2+>チャネルのAKAP依存性リン酸化が寄与する2011

    • Author(s)
      関口富美子, 松波真帆, 川畑篤史
    • Organizer
      第33回日本疼痛学会
    • Place of Presentation
      松山
    • Year and Date
      20110722-23
  • [Remarks]

    • URL

      http://www.phar.kindai.ac.jp/byoutai/

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Published: 2015-07-16  

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