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Mechanism of PACAP-induced tear secretion

Research Project

Project/Area Number 22791695
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Ophthalmology
Research InstitutionShowa University

Principal Investigator

NAKAMACHI Tomoya  昭和大学, 遺伝子組換え実験室, 助教 (30433840)

Co-Investigator(Renkei-kenkyūsha) SEKI Tamotsu  昭和大学, 医学部, 兼任講師 (10245855)
SHIODA Seiji  昭和大学, 医学部, 教授 (80102375)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords眼薬理学 / ドライアイ / 涙腺 / PACAP / 涙液分泌 / マウス
Research Abstract

The dry eye syndrome is one of the most common eye ailments caused by volume reduction or the altered quality of tears, however, an effective treatment has yet to be established. Our study was started based on the finding of a new phenotype in PACAP null mice, which show dry eye-like symptoms, corneal keratinization and tear reduction. PACAP and its receptor were expressed in mouse lacrimal glands, and PACAP eye drops stimulated tear secretion via an adenylate cyclase/cAMP/PKA cascade. PACAP stimulated aquaporin 5 translocation from the cytosol to the membrane in lacrimal acinar cells to induce tear secretion. These results suggest a possible role of PACAP as an endogenous regulator of tear secretion, and PACAP is a good candidate for an eye-drop medicine for the dry eye syndrome.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (44 results)

All 2012 2011 2010 Other

All Journal Article (17 results) (of which Peer Reviewed: 8 results) Presentation (24 results) Remarks (3 results)

  • [Journal Article] Role of PACAP in Neural Stem/Progenitor Cell and Astrocyte-From Neural Development to Neural Repair2011

    • Author(s)
      Nakamachi T, Farkas J, Watanabe J, Ohtaki H, Dohi K, Arata S, Shioda S
    • Journal Title

      Curr Pharm Des

      Volume: 17(10) Pages: 973-84

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide(PACAP) stimulates proliferation of reactive astrocytes in vitro2011

    • Author(s)
      Nakamachi T, Nakamura K, Oshida K, Kagami N, Mori H, Watanabe J, Arata S, Yofu S, Endo K, Wada Y, Hori M, Tsuchikawa D, Kato M, Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: 43(1) Pages: 16-21

    • Related Report
      2011 Final Research Report
  • [Journal Article] Suppression of rat retinal ganglion cell death by PACAP following transient ischemia induced by high intraocular pressure2011

    • Author(s)
      Seki T, Itoh H, Nakamachi T, Endo K, Wada Y, Nakamura K, Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: 43(1) Pages: 30-34

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] Neuroprotective effect of PACAP against NMDA-induced retinal damage in the mouse2011

    • Author(s)
      Endo K, Nakamachi T, Seki T, Kagami N, Wada Y, Nakamura K, Kishimoto K, Hori M, Tsuchikawa D, Shinntani N, Hashimoto H, Baba A, Koide R, Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: 43(1) Pages: 22-29

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates proliferation of reactive astrocytes in vitro2011

    • Author(s)
      Nakamachi T, Nakamura K, Oshida K, Kagami N, Mori H, Watanabe J, Arata S, Yofu S, Endo K, Wada Y, Hori M, Tsuchikawa D, Kato M, Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: 43(1) Issue: 1 Pages: 16-21

    • DOI

      10.1007/s12031-010-9404-3

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression and localization of the orexin-1 receptor (OX1R) after traumatic brain injury in mice2011

    • Author(s)
      Mihara Y, Dohi K, Yofu S, Nakamachi T, Ohtaki H, Shioda S, Aruga T
    • Journal Title

      J Mol Neurosci

      Volume: 43(2) Issue: 2 Pages: 162-8

    • DOI

      10.1007/s12031-010-9438-6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of interleukin-1 in lipopolysaccaride-induced microglial activation and learning and memory deficits2011

    • Author(s)
      Tanaka S, Kondo H, Kanda K, Ashino T, Nakamachi T, Sekikawa K, Iwakura Y, Shioda S, Numazawa S, Yoshida T
    • Journal Title

      J Neurosci Res

      Volume: 89 Issue: 4 Pages: 506-514

    • DOI

      10.1002/jnr.22582

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates proliferation of reactive astrocytes in vitro.2011

    • Author(s)
      Nakamachi T, Nakamura K, Oshida K, Kagami N, Mori H, Watanabe J, Arata S, Yofu S, Endo K, Wada Y, Hori M, Tsuchikawa D, Kato M, Shioda S.
    • Journal Title

      J Mol Neurosci

      Volume: 43(1) Pages: 16-21

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of rat retinal ganglion cell death by PACAP following transient ischemia induced by high intraocular pressure.2011

    • Author(s)
      Seki T, Itoh H, Nakamachi T, Endo K, Wada Y, Nakamura K, Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: 43(1) Pages: 30-34

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuroprotective effect of PACAP against NMDA-induced retinal damage in the mouse.2011

    • Author(s)
      Endo K, Nakamachi T, Seki T, Kagami N, Wada Y, Nakamura K, Kishimoto K, Hori M, Tsuchikawa D, Shinntani N, Hashimoto H, Baba A, Koide R, Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: 43(1) Pages: 22-29

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endogenous pituitary adenylate cyclase activating polypeptide is involved in suppression of edema in the ischemic brain2010

    • Author(s)
      Nakamachi T, Ohtaki H, Yofu S, Dohi K, Watanabe J, Mori H, Sato A, Hashimoto H, Shintani N, Baba A, Shioda S
    • Journal Title

      Acta Neurochir Suppl

      Volume: 106 Pages: 43-6

    • Related Report
      2011 Final Research Report
  • [Journal Article] Regulation of Oxidative Stress by Pituitary Adenylate Cyclase-Activating Polypeptide(PACAP) Mediated by PACAP Receptor2010

    • Author(s)
      Ohtaki H, Satoh A, Nakamachi T, Yofu S, Dohi K, Mori H, Ohara K, Miyamoto K, Hashimoto H, Shintani N, Baba A, Matsunaga M and Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: 42(3) Pages: 397-403

    • Related Report
      2011 Final Research Report
  • [Journal Article] Cardioprotective Effect of Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide on Doxorubicin-Induced Cardiomyopathy in Mice2010

    • Author(s)
      Mori H, Nakamachi T, Ohtaki H, Yofu S, Sato A, Endo K, Iso Y, Suzuki H, Takeyama Y, Shintani N, Hashimoto H, Baba A and Shioda S
    • Journal Title

      Circ J

      Volume: 74(6) Pages: 1183-90

    • NAID

      10026474818

    • Related Report
      2011 Final Research Report
  • [Journal Article] Cardioprotective effect of endogenous pituitary adenylate cyclase-activating polypeptide on Doxorubicin-induced cardiomyopathy in mice.2010

    • Author(s)
      Mori H, Nakamachi T, Ohtaki H, Yofu S, Sato A, Endo K, Iso Y, Suzuki H, Takeyama Y, Shintani N, Hashimoto H, Baba A, Shioda S
    • Journal Title

      Circ J.

      Volume: 74(6) Pages: 1183-90

    • NAID

      10026474818

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of oxidative stress by pituitary adenylate cyclase-activating polypeptide (PACAP) mediated by PACAP receptor.2010

    • Author(s)
      Ohtaki H, Satoh A, Nakamachi T, Yofu S, Dohi K, Mori H, Ohara K, Miyamoto K, Hashimoto H, Shintani N, Baba A, Matsunaga M, Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: 42(3) Pages: 397-403

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-6 and PACAP receptor expression and localization after global brain ischemia in mice

    • Author(s)
      Nakamachi T, Tsuchida M, Kagami N, Yofu S, Wada Y, Hori M, Tsuchikawa D, Yoshikawa A, Imai N, Nakamura K, Arata S and Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: (in press)

    • Related Report
      2011 Final Research Report
  • [Journal Article] Neuroprotective Effect of Endogenous PACAP on Spinal Cord Injury

    • Author(s)
      Tsuchikawa D, Nakamachi T, Tsuchida M, Wada Y, Hori M, Jozsef F, Yoshikawa A, Kagami N, Imai N, Shintani N, Hashimoto H, Atsumi T, and Shioda S
    • Journal Title

      J Mol Neurosci

      Volume: (in press)

    • Related Report
      2011 Final Research Report
  • [Presentation] PACAP誘導性の涙液分泌におけるアクアポリン5の役割2012

    • Author(s)
      中町智哉、会沢洋一、大滝博和、養父佐知子、関保、和田悦洋、荒田悟、新谷紀人、橋本均、馬場明道、塩田清二
    • Organizer
      第117回日本解剖学会総会・全国学術集会
    • Place of Presentation
      甲府
    • Related Report
      2011 Final Research Report
  • [Presentation] The retinoprotective effect of exogenous PACAP involves a modulation of retinal microglia/macrophage2011

    • Author(s)
      Wada Y, Nakamachi T, Endo K, Seki T, Ohtaki H, Tsuchikawa D, Hori M, Farkas J, Tsuchida M, Yoshikawa A, Kagami N, Imai N, Shioda S
    • Organizer
      The 10th international Symposium on VIP, PACAP and Related Peptides
    • Place of Presentation
      Eilat, Israel
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] PACAP stimulates the lacrimation via aquaporin 5 translocatoin in mouse2011

    • Author(s)
      Nakamchi T, Aizawa Y, Ohtaki H, Seki T, Wada Y, Kagami N, Arata S, Hashimoto H, Shintani N, Baba A, Farkas J, Reglodi D, Shioda S
    • Organizer
      The 10th internatlonal Symposium on VIP, PACAP and Related Peptides
    • Place of Presentation
      Eilat, Israel
    • Year and Date
      2011-12-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] PACAP receptor expression and its function in mouse reactive astrocytes2011

    • Author(s)
      Nakamachi T, Jozsef F, Kagami N, Wada Y, Hori M, Tsuchikawa D, Tsuchida M, Yoshikawa A, Imai N, Hata A, Atrata S, Shioda S
    • Organizer
      Symposium of the 20th Annual Meeting of The Israel Society for Neuroscience~Basic and Clinical Research of GPCRs~
    • Place of Presentation
      Eilat, Israel
    • Year and Date
      2011-12-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] The exogenous PACAP is possible modulater of the activation of retinal microglia/macrophage in the injury retina2011

    • Author(s)
      Wada Y, Nakamachi T, Endo K, Seki T, Ohtaki H, Tsuchikawa D, Hori M, Farkas J, Tsuchida M, Yoshikawa A, Kagami N, Imai N, Shioda S
    • Organizer
      Symposium of the 20th Annual Meeting of The Israel Society for Neuroscience~Basic and Clinical Research of GPCRs~
    • Place of Presentation
      Eilat, Israel
    • Year and Date
      2011-12-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on reactive astrocyte induced by brain damage in mice2011

    • Author(s)
      Nakamachi T, Nakamura K, Wada Y, Kagami N, Tsuchikawa D, Hori M, Imai N, Yoshikawa A, Seki T, Atrata S, Shioda S
    • Organizer
      41st Annual meeting Society for Neuroscience
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-11-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Expression of pituitary adenylate cyclase-activating polypeptide (PACAP) receptor expression on reactive astrocyte after brain ischemia2011

    • Author(s)
      Nakamachi T, Ohtaki H, Dohi K, Kagami N, Shioda S
    • Organizer
      The XVth International Symposium of Brain Edema and Cellular Injury (Brain Edema 2011)
    • Place of Presentation
      Tokyo
    • Year and Date
      2011-10-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] 神経幹細胞および神経腫瘍細胞の増殖調節に関する分子基盤2011

    • Author(s)
      中町智哉・塩田清二
    • Organizer
      昭和大学戦略的基盤研究事業
    • Place of Presentation
      東京(公開シンポジウム)
    • Year and Date
      2011-07-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] PACAP遺伝子欠損マウスにおける呼吸機能異常2011

    • Author(s)
      中町智哉、荒田悟、鬼丸洋、塩田清二
    • Organizer
      第88回日本生理学会大会 第116回日本解剖学会総会・全国学術集会 合同大会
    • Place of Presentation
      横浜(紙面発表)
    • Year and Date
      2011-03-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] PACAP receptor expression and its function in mouse reactive astrocytes2011

    • Author(s)
      Tomoya Nakamachi, Farkas Jozsef, Nobuyuki Kagami, Yoshihiro Wada, Motohide Hori, Daisuke Tsuchikawa, Masashi Tsuchida, Akira Yoshikawa, Nori Imai, Azusa Hata, Satoru Atrata, and Seiji Shioda
    • Organizer
      GPCR satellite symposium
    • Place of Presentation
      Eilat, Israel
    • Related Report
      2011 Final Research Report
  • [Presentation] PACAP STIMULATES THE LACRIMATION VIA AQUAPORIN 5 TRANSLOCATOIN IN MOUSE2011

    • Author(s)
      Nakamachi T, Aizawa Y, Ohtaki H, Seki T, Wada Y, Kagami N, Arata S, Hashimoto H, Shintani N, Baba A, Farkas J, Reglodi D and Shioda S
    • Organizer
      The 10th international Symposium on VIP, PACAP and Related Peptides
    • Place of Presentation
      Eilat, Israel
    • Related Report
      2011 Final Research Report
  • [Presentation] Effect of pituitary adenylate cyclase-activating polypeptide(PACAP) on reactive astrocyte induced by brain damage in mice2011

    • Author(s)
      Tomoya Nakamachi, Keisuke Nakamura, Yoshihiro Wada, Nobuyuki Kagami, Daisuke Tsuchikawa, Motohide Hori, Nori Imai, Akira Yoshikawa, Tamotsu Seki, Satoru Arata, and Seiji Shioda
    • Organizer
      The 41th Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      Washington, DC
    • Related Report
      2011 Final Research Report
  • [Presentation] PACAPによる涙液分泌促進作用機序の解析2011

    • Author(s)
      中町智哉・会沢洋一・大滝博和・関保・和田悦洋・加賀美信幸・荒田悟・塩田清二
    • Organizer
      第36回日本比較内分泌学会
    • Place of Presentation
      東京
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Expression of pituitary adenylate cyclase-activating polypeptide(PACAP) receptor expression on reactive astrocyte after brain ischemia in mice2011

    • Author(s)
      Tomoya Nakamachi, Hirokazu Ohtaki, Kenji Dohi, Nobuyuki Kagami, Satoru Arata and Seiji Shioda
    • Organizer
      The XVth International Symposium of Brain Edema and Cellular Injury(Brain Edema 2011)
    • Place of Presentation
      Tokyo
    • Related Report
      2011 Final Research Report
  • [Presentation] 涙液分泌機能低下を示すPACAP欠損マウスを用いた涙液分泌機構の解析2011

    • Author(s)
      中町智哉、会沢洋一、大滝博和、関保、和田悦洋、加賀美信幸、荒田悟、塩田清二
    • Organizer
      第58回日本実験動物学会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] Investigation Of Neuroprotective Effects Of PACAP Against NMDA-induced Retinal Damage in Mice2011

    • Author(s)
      Seki T, Nakamachi T, Endo K, Shioda S
    • Organizer
      ARVO(The Association for Research in Vision and Ophthalmology)
    • Place of Presentation
      Fortlauderdale, Fl.
    • Related Report
      2011 Final Research Report
  • [Presentation] PACAP遺伝子欠損マウスにおける呼吸機能異常2011

    • Author(s)
      中町智哉・荒田悟・鬼丸洋・塩田清二
    • Organizer
      第88回日本生理学会大会・第116回日本解剖学会総会・全国学術集会合同大会
    • Place of Presentation
      横浜
    • Related Report
      2011 Final Research Report
  • [Presentation] Retinal Protective Effect of Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Against NMDA-induced Damage in Mice2010

    • Author(s)
      Tomoya Nakamachi, Kimi Endo, Tamotsu Seki, Nobuyuki Kagami, Keisuke Nakamura, Yoshihiro Wada, Kouji Kishimoto, Jozsef Farkas, Satoru Arata, Seiji Shioda
    • Organizer
      5th International Peptide Symposium
    • Place of Presentation
      京都
    • Year and Date
      2010-12-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] Distribution of activity-dependent neuroprotective protein (ADNP) and PAC1 receptor in intact and ischemic mouse brain2010

    • Author(s)
      Tomoya Nakamachi, Kimi Endo, Tamotsu Seki, Nobuyuki Kagami, Keisuke Nakamura, Yoshihiro Wada, Kouji Kishimoto, Jozsef Farkas, Satoru Arata, Seiji Shioda
    • Organizer
      40th Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      サンディエゴ(USA)
    • Year and Date
      2010-11-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] Retinal Protective Effect of Pituitary Adenylate Cyclase-activating Polypeptide(PACAP) Against NMDA-induced Damage in Mice2010

    • Author(s)
      Nakamachi T, Endo K, Seki T, Kagami N, Nakamura K, Wada Y, Kishimoto K, Farkas J, Arata S, Shioda S
    • Organizer
      5th International Peptide Symposium(Kyoto
    • Place of Presentation
      Kyoto
    • Related Report
      2011 Final Research Report
  • [Presentation] マウスにおけるPACAPの涙液分泌促進効果2010

    • Author(s)
      中町智哉
    • Organizer
      第35回日本比較内分泌学会大会
    • Place of Presentation
      静岡
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Distribution of activity-dependent neuroprotective protein(ADNP) and PAC1 receptor in intact and ischemic mouse brain2010

    • Author(s)
      Nakamachi T, Kagami N, Yofu S, Endo K, Nakamura K, Wada Y, Hori M, Arata S, Shioda S
    • Organizer
      The 40th Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      San Diego, CA
    • Related Report
      2011 Final Research Report
  • [Presentation] Deficient of learning and memory in aged PACAP-deficient mice2010

    • Author(s)
      Shioda S, Nakamachi T, Ohtaki H, Arata S
    • Organizer
      7th Joint meeting of the European Neuropeptide Club and the Summer Neuropeptide Conference
    • Place of Presentation
      Pecs, Hungary
    • Related Report
      2011 Final Research Report
  • [Presentation] 新規ドライアイ疾患モデル動物としてのPACAP遺伝子欠損マウスの評価2010

    • Author(s)
      中町智哉、会沢洋一、大滝博和、関保、遠藤貴美、荒田悟、新谷紀人、橋本均、馬場明道、塩田清二
    • Organizer
      第57回日本実験動物学会
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.showa-u.ac.jp/sch/med/major/anat-1/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.showa-u.ac.jp/sch/med/major/anat-1/rsch_achievement/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www10.showa-u.ac.jp/~anat-1/index.html

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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