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Regulatory mechanism of P2X7 receptor by its splice variants, and relationship of its altered functional expression to psychiatric diseases

Research Project

Project/Area Number 24590128
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

NAGASAWA Kazuki  京都薬科大学, 薬学部, 教授 (30228001)

Co-Investigator(Kenkyū-buntansha) NISHIDA Kentaro  京都薬科大学, 薬学部, 助教 (20533805)
松尾 剛明  京都薬科大学, 薬学部, 助教 (60612702)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsATP / 脳・神経 / 受容体 / P2X7 / アストロサイト / スプライスバリアント / 食作用
Outline of Final Research Achievements

The activity of P2X7 receptors expressed in cultured astrocytes of SJL-strain mice, which exhibit extremely aggression characteristics, was greater than the case of ddY-strain mice, and this was due to the less expression levels of P2X7 receptor splice variant 2 and 3 in the formers. In addition, we demonstrated that spontaneous activation of P2X7Rs expressed by astrocytes plays a role in regulation of engulfing activity of astrocytes. Finally, we found that in activated astrocytes, which was induced by stress-load such as oxidative stress, expression of P2X7 receptors at the plasma membrane was decreased by increased expression of its splice variant 2 and 3, resulting in decreased engulfing activity. These findings indicated that P2X7 receptor is regulated by expression levels of its splice variants, and its activity plays a role in regulation of astrocytic functionality.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (47 results)

All 2015 2014 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Acknowledgement Compliant: 2 results) Presentation (39 results)

  • [Journal Article] The effect of divalent metal cations on zinc uptake by mouse Zrt/Irt-like protein 1 (ZIP1)2014

    • Author(s)
      Segawa et al.
    • Journal Title

      Life Sciences

      Volume: 113 Issue: 1-2 Pages: 40-44

    • DOI

      10.1016/j.lfs.2014.07.030

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Astrocytes, but Not Neurons, Exhibit Constitutive Activation of P2X7 Receptors in Mouse Acute Cortical Slices under Non-stimulated Resting Conditions2014

    • Author(s)
      Kamatsuka et al.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 37 Issue: 12 Pages: 1958-1962

    • DOI

      10.1248/bpb.b14-00000

    • NAID

      130004703918

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Zinc is released by cultured astrocytes as a gliotransmitter under hypoosmotic stress-loaded conditions and regulates microglial activity.2014

    • Author(s)
      Segawa S, Nishiura T, Furuta T, Ohsato Y, Tani M, Nishida K, Nagasawa K.
    • Journal Title

      Life Science

      Volume: 94 Issue: 2 Pages: 137-144

    • DOI

      10.1016/j.lfs.2013.11.007

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of activity of P2X7 receptor by its splice variants in cultured mouse astrocytes2014

    • Author(s)
      Kido Y, Kawahara C, Terai Y, Ohishi A, Kobayashi S, Hayakawa M, Kamatsuka Y, Nishida K, Nagasawa K.
    • Journal Title

      Glia

      Volume: 62 Issue: 3 Pages: 440-451

    • DOI

      10.1002/glia.22615

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] P2X7 receptors regulate engulfing activity of non-stimulated resting astrocytes.2013

    • Author(s)
      Yamamoto M, Kamatsuka Y, Ohishi A, Nishida K, Nagasawa K.
    • Journal Title

      BBRC

      Volume: 439 Issue: 1 Pages: 90-95

    • DOI

      10.1016/j.bbrc.2013.08.022

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] NAD+ influx through connexin hemichannels prevents poly(ADP-ribose) polymerase-mediated astrocyte death.2013

    • Author(s)
      Okuda H, Nishida K, Higashi Y, Nagasawa K.
    • Journal Title

      Life Science

      Volume: 92 Issue: 13 Pages: 808-814

    • DOI

      10.1016/j.lfs.2013.02.010

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expression of equilibrative nucleoside transporter 1 in rat circumvallate papillae2013

    • Author(s)
      Nishida K, Kitada T, Kato J, Dohi Y, Nagasawa K.
    • Journal Title

      Neuroscience Letters

      Volume: 533 Pages: 104-108

    • DOI

      10.1016/j.neulet.2012.10.063

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial dysfunction is involved in P2X7 receptor-mediated neuronal cell death.2012

    • Author(s)
      Nishida K
    • Journal Title

      J. Neurochemistry

      Volume: 122 Issue: 6 Pages: 1118-1128

    • DOI

      10.1111/j.1471-4159.2012.07868.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 酸化ストレス負荷されたアストロサイトにおけるP2X7受容体の機能低下は細胞内遊離型亜鉛の増大に起因する2015

    • Author(s)
      向井あゆみら
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] SJL系及びddY系マウス大脳皮質神経細胞におけるP2X7受容体の機能的発現の比較2014

    • Author(s)
      丸宮ら
    • Organizer
      第64回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 酸化ストレス負荷されたアストロサイトにおけるengulfment活性の低下はP2X7受容体の局在変化に起因する2014

    • Author(s)
      山本ら
    • Organizer
      第64回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 活性化アストロサイトにおけるP2X7受容体の機能的発現変動について2014

    • Author(s)
      古田ら
    • Organizer
      第57回日本神経化学会大会・第36回日本生物学的精神医学会 合同年会
    • Place of Presentation
      奈良
    • Year and Date
      2014-09-29 – 2014-10-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] P2X7 receptors regulate engulfing activity of non-stimulated resting astrocytes2014

    • Author(s)
      Nagasawa et al.
    • Organizer
      Purines2014
    • Place of Presentation
      Bonn
    • Year and Date
      2014-07-23 – 2014-07-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] アストロサイトに発現するP2X7受容体によるengulfment活性の制御2013

    • Author(s)
      山本美菜ら
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] ラットの甘味感受性に対するオキサリプラチンの影響2013

    • Author(s)
      西田健太朗ら
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] マウス初代培養大脳皮質アストロサイト及びミクログリアにおける亜鉛取り込み特性の比較2013

    • Author(s)
      瀬川将平ら
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] マウス大脳皮質神経細胞におけるATP誘発性神経細胞死のP2X7受容体の関与について2013

    • Author(s)
      藤本真知子ら
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Oxaliplatin投与ラットにおける甘味感受性の変化について2013

    • Author(s)
      西田健太朗ら
    • Organizer
      日本味と匂学会第47回大会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] Oxaliplatinによる味覚障害発症機序の基礎的検討 ~味受容体の発現及び味細胞数への影響~2013

    • Author(s)
      西田健太朗ら
    • Organizer
      第86回日本生化学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 活性化アストロサイトにおける亜鉛クリアランス機構の機能的発現について2013

    • Author(s)
      須藤嵩史ら
    • Organizer
      メタルバイオサイエンス研究会2013
    • Place of Presentation
      静岡
    • Related Report
      2013 Research-status Report
  • [Presentation] 亜鉛トランスポータZrt-and Irt-like protein 1 (ZIP1) 過剰発現系の構築とその機能評価2013

    • Author(s)
      瀬川将平ら
    • Organizer
      メタルバイオサイエンス研究会2013
    • Place of Presentation
      静岡
    • Related Report
      2013 Research-status Report
  • [Presentation] 味細胞には亜鉛トランスポータZnT3が発現する2013

    • Author(s)
      西田健太朗ら
    • Organizer
      メタルバイオサイエンス研究会2013
    • Place of Presentation
      静岡
    • Related Report
      2013 Research-status Report
  • [Presentation] マウス急性脳切片を用いた大脳皮質アストロサイトに発現するP2X7受容体の機能的発現について2013

    • Author(s)
      鎌塚洋祐ら
    • Organizer
      第63回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] マウスアストロサイトに発現するP2X7受容体はそのsplice variants 3 及び4によって制御される2013

    • Author(s)
      早川美紀ら
    • Organizer
      第63回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] 活性化アストロサイトにおける亜鉛トランスポータZIPアイソフォームの発現並びに機能性について2013

    • Author(s)
      竹林直人ら
    • Organizer
      第63回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] ラット味蕾のII型及びIII型味細胞における亜鉛トランスポータZnT3の発現解析2013

    • Author(s)
      生川晃子ら
    • Organizer
      第63回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Oxaliplatin投与ラットにおける味蕾の免疫組織学的及び味覚の行動学的解析2013

    • Author(s)
      藪美晴ら
    • Organizer
      第63回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Presentation] Sweet taste receptor expression is upregulated in oxaliplatin-administered rats2013

    • Author(s)
      Kentaro Nishida et al.
    • Organizer
      The 11th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception (YR Umami Forum 2013, AISCRIB 2013)
    • Place of Presentation
      Fukuoka
    • Related Report
      2013 Research-status Report
  • [Presentation] ラットのうま味感受性に対するoxaliplatinの影響2013

    • Author(s)
      宮田麻依ら
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Oxaliplatin投与ラットにおける味受容体の発現及び味感受性への影響2013

    • Author(s)
      山中優里ら
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 亜鉛トランスポータZrt- and Irt-like protein 1(ZIP1)過剰発現系の構築とその機能評価2013

    • Author(s)
      芝本真紀子ら
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 知覚神経細胞-衛星細胞間における細胞外ATP代謝機構の解明2013

    • Author(s)
      河盛佳那子ら
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] ラット有郭乳頭におけるヌクレオチド代謝酵素の発現解析2013

    • Author(s)
      松本沙希ら
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 初代培養マウスアストロサイトのengulfment活性制御へのP2X7受容体の関与について2013

    • Author(s)
      山本美菜ら
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 中枢神経抑制薬の併用によりプレガバリンの副作用発現は上昇する2013

    • Author(s)
      大石晃弘ら
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] マウス初代培養大脳皮質アストロサイト及びミクログリアにおける亜鉛輸送特性の比較2013

    • Author(s)
      瀬川将平ら
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] マウス大脳皮質神経細胞におけるP2X7受容体の機能的発現について2013

    • Author(s)
      鎌塚洋祐ら
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] マウスアストロサイトに発現するP2X7受容体splice variant 3及び4はその活性制御因子である2013

    • Author(s)
      小林哲ら
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] P2X7 receptor channel opening is regulated by its splice variants in cultured mouse astrocytes2012

    • Author(s)
      Yasuko Terai et al.
    • Organizer
      Purine 2012
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Expression profile of ecto-nucleotidases and equilibrative nucleoside transporter in the rat circumvallate papillae2012

    • Author(s)
      Kentaro Nishida et al.
    • Organizer
      Purine 2012
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Expression profile of P2X7 receptor splice variants is a determinant for P2X7 receptor functionality in cultured astrocytes2012

    • Author(s)
      Kazuki Nagasawa et al.
    • Organizer
      The 11th Biennial Meeting of the Asian-Pacific Society for Neurochemistry / 55th Annual Meeting of the Japanese Society for Neurochemistry
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] Expression Profile of ecto-nucleotidases and adenosine receptors in rat circumvallate papillae2012

    • Author(s)
      Kentaro Nishida et al.
    • Organizer
      The 11th Biennial Meeting of the Asian-Pacific Society for Neurochemistry / 55th Annual Meeting of the Japanese Society for Neurochemistry
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] ラット有郭乳頭におけるATP分解酵素の発現解析2012

    • Author(s)
      西田健太朗ら
    • Organizer
      日本味と匂学会第46回大会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] ラット有郭乳頭におけるecto-nucleotide pyrophosphatase/phosphodiesterases (ENPPs) の発現解析

    • Author(s)
      久保田晃代ら
    • Organizer
      第62回日本薬学会 近畿支部総会・大会
    • Place of Presentation
      西宮
    • Related Report
      2012 Research-status Report
  • [Presentation] アストロサイトに発現するP2X7受容体のsplice variantsによる活性制御

    • Author(s)
      松浦未工ら
    • Organizer
      第62回日本薬学会 近畿支部総会・大会
    • Place of Presentation
      西宮
    • Related Report
      2012 Research-status Report
  • [Presentation] ラット脊髄後根神経節におけるorganic cation/carnitine transporters OCTN1及びOCTN2の発現解析

    • Author(s)
      森﨑恵理ら
    • Organizer
      第62回日本薬学会 近畿支部総会・大会
    • Place of Presentation
      西宮
    • Related Report
      2012 Research-status Report
  • [Presentation] P2X7受容体を介した神経細胞死におけるミトコンドリア機能異常の関与

    • Author(s)
      西田健太朗ら
    • Organizer
      第62回日本薬学会 近畿支部総会・大会
    • Place of Presentation
      西宮
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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