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Physiological and Pathophysiological roles of prostanoids revealed from studies using mice lacking their receptors

Research Project

Project/Area Number 11694269
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionAsahikawa Medical College

Principal Investigator

USHIKUBI Fumitaka  Asahikaw Medical College, Pharmacology, Professor, 医学部, 教授 (50243035)

Co-Investigator(Kenkyū-buntansha) KOBAYASHI Takuya  Kyoto University, Pharmacology, Assistant Professor, 医学部, 助手 (20311730)
BITO Haruhiko  Kyoto University, Pharmacology, Lecturer, 医学部, 講師 (00291964)
HARA Akiyoshi  Asahikaw Medical College, Pharmacology, Associate Professor, 医学部, 助教授 (90164988)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2000: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥3,500,000 (Direct Cost: ¥3,500,000)
Keywordsprostanoids / prostaglandin / knockout mice / prostanoid receptor / fertilization / allergic asthma / platelets / ischemia-reperfusipn / トロンボキサン / 中枢神経機能 / 肺高血圧症 / 気管支喘息 / 大腸癌
Research Abstract

The prostanoids are lipid mediators showing variable effects on many organs. Theirphysiological and pathophysiological roles in the body, however, have been largely unknown. We attmpted to clarify these roles using mice lacking the prostanoids receptors individually, and found several novel and important roles of prostanoids. They include a cardioprotective role of prostaglandin (PG)l_2 in ischemia-reperfusion injury, roles of PGE_2 via the EP_3 receptor in hemostasis, thromboembolism and alkari secretion in the duodenum, a role of PGD_2 as a mediator of allergic asthma, participation of PGE_2 via the EP_1 and EP_2 receptors in the carcinogenesis of colon, a regulatory role of PGE_2 via the EP_2 receptor of ovulation ad fertilization and a role of PGE_2 via the EP_4 receptor in bone resorption. Furthermore, other roles of prostanoids have been being clarified in many systems, such as central nervous, immune, cardiovascular and gastrointestinal systems. These results would contribute to the development of novel drugs able to control many pathological conditions, in which prostanoids have major roles.

Report

(3 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Hizaki, H.: "Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP_2."Proc. Nati. Acad.Sci. U. S. A.. 96. 10501-10506 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narumiya, S.: "Prostanoid receptors: structures, properties and functions"Physiol. Rev.. 79. 1193-1226 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeuchi, K.: "Impaired duodenal bicarbonate secretion and mucosal integrity in mice lacking prostaglandin E-receptor subtype EP_3."Gastroenterology. 117. 1128-1135 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Waranabe, K.: "Role of the prostaglandin E receptor subtype EP_1 in colon carcinogenesis"Cancer Res.. 59. 5093-5096 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsuoka, T.: "Prostaglandin D_2 as a mediator of allergic asthma"Science. 287. 2013-2017 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sonoshita, M.: "Acceleration of intestinal polyposis through prostaglandin receptor EP2 in Apc 716 knockout mice"Nat. Med.. 7. 1048-1051 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hizaki, H. et al.: "Abortive expansion of the cumulus and impairedfertility in mice lacking the prostaglandin E receptor subtype EP_2"Proc. Natl. Acad. Sci. U. S. A.. 96. 10501-10506 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narumiya, S. et al.: "Prostenoid receptors: structures, properties and functions"Physiol. Rev.. 79. 1193-1226 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takeuehi , K. et al.: "Impaired duodenal bicarbonate secretion and mucosal integrity in mice lacking prpstaglandin E-receptqr subtype EP_3"Gastroenterology. 117. 1128-1135 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Watanabe, K. et al.: "Role of the prostaglandin E receptor subtype EP_1 in colon carcinogenesisole of the prostaglandin E receptor subtype EP_1 in colon carcinogenesis"Cancer Res.. 59. 5093-5096 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Matsuoka, T. et al.: "Prostaglandin D_2 as a mediator of allergic asthma"Science. 287. 2013-2017 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sonoshita, M. et al.: "Acceleration of intestinal polyposis through prostagladin receptor EP_2 in Apc^<Δ716> knockout mice"Nature Med.. 7. 1048-1051 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Okada,Y. et al.: "Characterization of prostanoid receptors mediating contraction of the gastric fundus and ileum : Studies using mice deficient in prostanoid receptors."Br.J.Pharmacology. 131. 745-755 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ushikubi,F. et al.: "Roles of prostanoids revealed from studies using mice lacking specific prostanoid receptors."Jpn.J.Pharmacol.. 83. 279-285 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakuma,Y. et al.: "Impaired bone resorption by lipopolysaccharide in vivo in mice deficient in the prostaglandin E receptor EP4 subtype."Infect.Immun.. 68. 6819-6825 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyaura,C. et al.: "Impaired bone resorption to prostaglandin E_2 in prostaglandin E receptor EP_4-knockout mice."J.Biol.Chem.. 275. 19819-19823 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsuoka,T. et al.: "Prostaglandin D_2 as a mediator of allergic asthma."Science. 287. 2013-2017 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suzawa,T. et al.: "The role of prostaglandin E receptor subtypes (EP1,EP2,EP3,and EP4) in bone resorption : an analysis using specific agonists for the respective EPs."Endocrinology. 141. 1554-1559 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakuma,Y. et al.: "Crucial involvement of the EP4 subtype of prostaglandin E receptor in osteoclast formation by proinflammatory cytokines and lipopolysaccharide."J.Bone.Miner.Res.. 15. 218-227 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Watanabe,K. et al.: "Role of the prostaglandin E receptor subtype EP_1 in colon carcinogenesis."Cancer Res.. 59. 5093-5096 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeuchi,K. et al.: "Impaired duodenal bicarbonate secretion and mucosal integrity in mice lacking prostaglandin E-receptor subtype EP_3."Gastroenterology. 117. 1128-1135 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Narumiya,S. et al.: "Prostanoid receptors : structures, properties and functions."Physiol.Rev.. 79. 1193-1226 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hizaki,H. et al.: "Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP_2."Proc.Natl.Acad.Sci.U.S.A.. 96. 10501-10506 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hizaki H., et al.: "Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP2"Proc. Natl. Acad. Sci. U.S.A.. 96. 10501-10506 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Narumiya S., et al.: "Prostanoid receptors : structures, properties and functions"Physiol. Rev.. 79. 1193-1226 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takeuchi K. et al.: "Impaired duodenal bicarbonate secretion and mucosal integrity in mice lacking prostaglandin E-receptor subtype EP3"Gastroenterology. 117. 1128-1135 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Watanabe K., et al.: "Role of the prostaglandin E receptor subtype EP1 in colon carcinogenesis"Cancer Res.. 59. 5093-5096 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakuma Y., et al.: "Crucial involvement of EP4 subtype of prostaglandin E receptor in osteoclast formation by proinflammatory cytokines and lipopolysaccharide"J. Bone. Miner. Res.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsuoka T., et al.: "Prostaglandin D2 as a mediator of allergic asthma"Science. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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