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Pathophysiologic significance of PACAP in hypothalamus

Research Project

Project/Area Number 25461390
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionKagoshima University

Principal Investigator

Miyata Atsuro  鹿児島大学, 医歯学域医学系, 教授 (60183969)

Co-Investigator(Kenkyū-buntansha) INOUE Kazuhiko  鹿児島大学, 医歯学域医学系, 助教 (30363641)
KAMBE Yuki  鹿児島大学, 医歯学域医学系, 助教 (60549913)
Co-Investigator(Renkei-kenkyūsha) KATSUURA Goro  鹿児島大学, 医歯学総合研究科, 特任講師 (20401226)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsPACAP / 視床下部 / 摂食 / glycogen / アストロサイト / 生理活性ペプチド / 神経内分泌 / 下垂体
Outline of Final Research Achievements

Pituitary adenylate cyclase activating polypeptide (PACAP) is localized in hypothalamus with highest concentration. To evaluate PACAP function as a hypothalamic factor, we attempted to elucidate the regulatory mechanism of gene expression of PACAP specific receptor, PAC1. Further we tried to evaluate the function of PACAP in appetite control and energy metabolism by using PACAP-knock out (KO) mice. As a result, we found that the expression of PAC1 is negatively regulated by ER stress. As regarding glycogen metabolism, PACAP potentiates not only glycogenolysis but also glycogensesis of astrocytes. In the analysis of PACAP KO mice, their food intake were significantly decreased and the gene expression of PACAP in PACAP KO mice were significantly increased by fasting. During refeeding, the increments of gene expression of NPY and AgRP, orexigenic peptides were cancelled in PACAP KO mice. These suggest orexigenic function of PACAP in appetite control.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (36 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 4 results,  Acknowledgement Compliant: 6 results) Presentation (22 results)

  • [Int'l Joint Research] カロリンスカ研究所(スウェーデン)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Pituitary and adenylate cyclase-activating polypeptode type 1 receptor signaling evokes long-lasting nociceptive behavior through the activation of spinal astrocytes in mice,2016

    • Author(s)
      Ohnou T, Yokai M, Hasegawa-Moriyama M, Shimizu T, Inoue K, Kambe Y, Kanmura Y, Miyata A
    • Journal Title

      Journal of Phamacological Sciences

      Volume: 1 Issue: 4 Pages: 1-10

    • DOI

      10.1016/j.jphs.2016.01.008

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Spinal astrocyteic activation contribites to both induction and maintenance of pituitary adenylate cyclase-activating polypeptyde type 1 receptor-induced long-lasting mechanical allodynia in mice2016

    • Author(s)
      Masafumi Yokai, Takashi Kurihara, Atsuro Miyata
    • Journal Title

      Molecular Pain

      Volume: 12 Pages: 1-13

    • DOI

      10.1177/1744806916646383

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mitochondrial c-Fos May Increase the Vulnerability of Neuro2a Cells to Cellular Stressors2016

    • Author(s)
      Kambe Y, Miyata A
    • Journal Title

      Journal of Molecular Neuroscience

      Volume: 59 Issue: 1 Pages: 106-112

    • DOI

      10.1007/s12031-015-0710-7

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Involvement of free fatty acid receptor GPR40/FFAR1 in the regulation of spinal nociceptive transmission2015

    • Author(s)
      栗原 崇、宮田 篤郎
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 146 Issue: 6 Pages: 309-314

    • DOI

      10.1254/fpj.146.309

    • NAID

      130005129755

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Potential involvement of the mitochondrial unfolded protein response in depressive-like symptoms in mice2015

    • Author(s)
      Kambe, Y, Miyata, A
    • Journal Title

      Neurosci Lett

      Volume: 588 Pages: 166-171

    • DOI

      10.1016/j.neulet.2015.01.006

    • NAID

      130007812003

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Attenuation of inflammatory and neuropathic pain behaviors in mice through activation of free fatty acid receptor GPR40.2015

    • Author(s)
      Karki P, Kurihara T, Nakamachi T, Watanabe J, Asada T, Oyoshi T, Shioda S, Yoshimura M, Arita K, Miyata A.
    • Journal Title

      Mol Pain.

      Volume: 11(1) Pages: 6-6

    • DOI

      10.1186/s12990-015-0003-8

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional Characterization of Neural-Restrictive Silencer Element in Mouse Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Gene Expression2014

    • Author(s)
      Sugawara H, Tominaga A, Inoue K, Takeda Y, Yamada K, Miyata A
    • Journal Title

      J Mol Neurosci

      Volume: 54 Issue: 3 Pages: 526-534

    • DOI

      10.1007/s12031-014-0348-x

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Development and pharmacological verification of a new mouse model of central post-stroke pain.2014

    • Author(s)
      Hanada T, Kurihara T, Tokudome M, Tokimura H, Arita K, Miyata A.
    • Journal Title

      Neurosci Res.

      Volume: 78 Pages: 72-80

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] C-type natriuretic peptide modulates permeability of the blood-brain barrier.2014

    • Author(s)
      Bohara M, Kambe Y, Nagayama T, Tokimura H, Arita K, Miyata A
    • Journal Title

      J Cereb Blood Flow Metab.

      Volume: 34(4) Pages: 589-96

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alleviation of behavioral hypersensitivity in mouse models of inflammatory pain with two structurally different casein kinase 1 (CK1) inhibitors.2014

    • Author(s)
      Kurihara T, Sakurai E, Toyomoto M, Kii I, Kawamoto D, Asada T, Tanabe T, Yoshimura M, Hagiwara M, Miyata A.
    • Journal Title

      Mol Pain

      Volume: 10 Pages: 10-17

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) gene is suppressed by transglutaminase 2 activation.2013

    • Author(s)
      Miura A, Kambe Y, Inoue K, Tatsukawa H, Kurihara T, Griffin M, Kojima S, Miyata A.
    • Journal Title

      J. Biol. Chem.

      Volume: 288(45) Pages: 32720-30

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Muscle wasting associated with pathologic change is a risk factor for the exacerbation of joint swelling in collagen-induced arthritis in cynomolgus monkeys.2013

    • Author(s)
      Horai N, Nagaoka T, Higuchi I, Kasai H, Yoshioka T, Umekita Y, Fukuzaki K, Nagata R, Miyata A, Abeyama K.
    • Journal Title

      BMC Musculoskelet Disord.

      Volume: 14(1) Pages: 205-205

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A combination of in vitro comet assay and micronucleus test using human lymphoblastoid TK6 cells.2013

    • Author(s)
      Kimura A, Miyata A, Honma M.
    • Journal Title

      Mutagenesis.

      Volume: 28(5) Pages: 583-590

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] PACAP-PAC1受容体を介した脊髄アストロサイト活性化は長期機械的アロディニアの誘発および維持両者に寄与する2016

    • Author(s)
      用皆正文、栗原崇、宮田篤郎
    • Organizer
      第89回 日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県 横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 脊髄アストロサイトーニューロン乳酸シャトルはPACAP誘発長期機械的アロディニア発症に寄与する2016

    • Author(s)
      神戸悠輝、栗原崇、用皆正文、前田辰則、高崎一朗、宮田篤郎
    • Organizer
      第89回 日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県 横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 脊髄Cyr61はPACAP及びMaxadilan誘導性の長期アロディニア反応に寄与する2016

    • Author(s)
      前田辰則、中西秀行、用皆正文、宮田篤郎、栗原崇、高崎一朗
    • Organizer
      第89回 日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県 横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 新規鎮痛薬の開発を目指したPAC1受容体アンタゴニストの創出と薬理学的評価2016

    • Author(s)
      渡辺藍、岡田卓哉、福地守、合田浩明、宮田篤郎、栗原崇、豊岡尚樹、高崎一朗
    • Organizer
      第89回 日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜 (神奈川県 横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] 脊髄内PACAP-PAC1受容体シグナルはアストロサイト活性化を介して機械的アロディニアの発症と維持両者に寄与する2015

    • Author(s)
      用皆正文、栗原崇、宮田篤郎
    • Organizer
      第68回 日本薬理学会西南部会
    • Place of Presentation
      海峡メッセ下関(山口県 下関市)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 遊離中/長鎖脂肪酸受容体GPR40/FFAR1の脊髄痛覚伝達における役割2015

    • Author(s)
      栗原崇、カルキ・プラサンナ、中町智哉、渡邊潤、朝田俊秀、大吉達樹、塩田清二、吉村恵、有田和徳、宮田篤郎
    • Organizer
      第12回 GPCR研究会
    • Place of Presentation
      日本科学未来館 (東京都 品川区)
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 下垂体アデニル酸シクラーゼ活性化ペプチドによる脳内グリコーゲン代謝の活性化2015

    • Author(s)
      神戸悠輝、中島優、新谷紀人、橋本均、宮田篤郎
    • Organizer
      第12回 GPCR研究会
    • Place of Presentation
      日本科学未来館 (東京都 品川区)
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 脊髄内PACAP-PAC1受容体シグナルはアストロサイト活性化を介して長期機械的アロディニアを誘発する2015

    • Author(s)
      用皆正文、栗原崇、神戸悠輝、高﨑一朗、宮田篤郎
    • Organizer
      第12回 GPCR研究会
    • Place of Presentation
      日本科学未来館 (東京都 品川区)
    • Year and Date
      2015-05-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] 培養アストロサイトにおける下垂体アデニル酸シクラーゼ活性化ポリペプチドによるグリコーゲン代謝の活性化2015

    • Author(s)
      神戸悠輝、中島優、新谷紀人、橋本均、宮田篤郎
    • Organizer
      第88回日本薬理学年会
    • Place of Presentation
      名古屋 名古屋国際会議場
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 脊髄におけるPACAP特異的受容体の刺激はアストロサイト活性化を介して長期機械的アロディニア反応を誘発する2015

    • Author(s)
      用皆正文、栗原崇、神戸悠輝、高崎一郎、宮田篤郎
    • Organizer
      第88回日本薬理学年会
    • Place of Presentation
      名古屋 名古屋国際会議場
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 有痛性神経障害患者血清のマウスへの受動的移入による疼痛様行動再現の試み2015

    • Author(s)
      栗原崇、福留学、宮田篤郎、結城伸泰
    • Organizer
      第88回日本薬理学年会
    • Place of Presentation
      名古屋 名古屋国際会議場
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 下垂体アデニル酸シクラーゼ活性化ポリペプチドによる脳内グリコーゲン代謝の活性化~培養アストロサイトを用いた研究~2014

    • Author(s)
      神戸悠輝、宮田篤郎
    • Organizer
      第67回日本薬理学会西南部会
    • Place of Presentation
      北九州市 産業医科大学
    • Year and Date
      2014-11-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 有痛性神経障害患者血清のマウスへの受動態移入による疼痛様行動の再現2014

    • Author(s)
      福留学、井上隆之、宮田篤郎、結城伸泰、栗原崇
    • Organizer
      第67回日本薬理学会西南部会
    • Place of Presentation
      北九州市 産業医科大学
    • Year and Date
      2014-11-23
    • Related Report
      2014 Research-status Report
  • [Presentation] 下垂体腺腫細胞GH3のプロラクチンおよび成長ホルモン分泌に及ぼすリゾホスファチジルセリンの効果2014

    • Author(s)
      井上和彦、竹ノ内里奈、國師恵美子、大和麻耶、神戸悠輝、宮田篤郎
    • Organizer
      第67回日本薬理学会西南部会
    • Place of Presentation
      北九州市 産業医科大学
    • Year and Date
      2014-11-23
    • Related Report
      2014 Research-status Report
  • [Presentation] Spinal PACAP-PAC1-receptor signaling pathway induces long-lasting mechanical allodynia through the activation of astrocytes in mice2014

    • Author(s)
      Youkai M, Kurihara T, Asada T, Kambe Y, Inoue K, Miyata A
    • Organizer
      Society for Neuroscience 2014
    • Place of Presentation
      米国・ワシントン
    • Year and Date
      2014-11-20 – 2014-11-25
    • Related Report
      2014 Research-status Report
  • [Presentation] 脳虚血におけるPAC1遺伝子発現の抑制メカニズム2014

    • Author(s)
      宮田篤郎、三浦綾子、神戸悠輝、辰川英樹、栗原崇、小嶋聡一
    • Organizer
      第11回GPCR研究会
    • Place of Presentation
      東京 日本科学未来館
    • Year and Date
      2014-05-09 – 2014-05-10
    • Related Report
      2014 Research-status Report
  • [Presentation] 脊髄疼痛伝達における遊離脂肪酸受容体GPR40の関与2014

    • Author(s)
      栗原 崇、カルキ・プラサンナ、朝田俊秀、吉村惠、有田和徳、宮田篤郎
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] トランスグルタミナーゼ2によるPACAP特異的受容体PAC1の遺伝子発現抑制メカニズム2014

    • Author(s)
      宮田篤郎、三浦綾子、神戸悠輝、小嶋聡一
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Research-status Report
  • [Presentation] PACAPによる神経突起伸展促進作用におけるミトコンドリアの寄与2013

    • Author(s)
      神戸悠輝、宮田篤郎
    • Organizer
      第15回ブレインサイエンス研究会
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] Acute activation of astrocytes in spinal dorsal horn VIP PAC1 receptor is involved in PACAP-induced persistent aversive behavior.2013

    • Author(s)
      Miyata A, Yokai M, Ohno T, Hasegawa M, Kambe Y, Inoue K, Kamimura Y, Shimizu T, Kurihara T.
    • Organizer
      The 11th International Symposium on VIP,PACAP and Related Peptides,
    • Place of Presentation
      Pecs, HUNGARY
    • Related Report
      2013 Research-status Report
  • [Presentation] C-type natriuretic peptide modulates permeability of the blood-brain barrier.2013

    • Author(s)
      Bohara M, Kambe Y, Kurihara T, Nagayama T, Tokimura H, Arita K, Miyata A
    • Organizer
      Annual Meeting of Society for Nueroscience,
    • Place of Presentation
      San Diego USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Cross-linking of SP1 by transglutaminase2 suppresses PAC1 gene expression in neuronal cells.2013

    • Author(s)
      Miyata A, Miura A, Kambe Y, Kojima S.
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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