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Roles of prostanoids in cardiovascularsystem revealed from studies using knockout mice

Research Project

Project/Area Number 11470020
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  Asahikawa Medical College, Pharmacology, Professor, 医学部, 教授 (50243035)

Co-Investigator(Kenkyū-buntansha) HARA Akiyoshi  Asahikavva 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
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2000: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1999: ¥7,600,000 (Direct Cost: ¥7,600,000)
Keywordsprostanoids / prostaglandin / thromboxane / knockout mice / prostanoid receptor / cardiovascular system / platelets / ischemia-reperfusion / 循環器 / 心筋虚血 / 心肥大
Research Abstract

The prostanoids are lipid mediators showing variable effects on many organs in the body including the cardiovascular system. Their roles in the system, however, have been largely unknown. We attempted to clarify these roles using mice lacking the prostanoids receptors individually. We first established variable methods for the analysis. These include in vivo models such as for cardiac hypertrophy, thromboembolism, vascular remodeling and renovascular hypertension, and in vitro systems for culture of vascular smooth muscle cells, cultures of cardiomyocytes from fetal or adult mice, platelet aggregation and vascular tone. We next examined the roles of the prostanoids using the established methods and knockout mice, Prostaglandin (PG)l_2 was found to be a potent mediator to protect the cardiomyocytes from ischemia-reperfusion injury. PGE_2 potentiated the platelet activation induced by other platelet stimulants, such as thromboxane A_2 and ADP. Furthermore, this potentiating effect on the platelets was verified to be important in both hemostasis and thromboembolism. Other roles of the prostanoids in the cardiovascular system would be clarified in near future, because several interesting results have been already obtained in the present project. They include the roles in various pathological conditions such as cardiac hypertrophy, vascular remodeling and renovascular hypertension

Report

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

    (20 results)

All Other

All Publications (20 results)

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

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

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ma, H.: "Increased bleeding tendency and decreased susceptibility to thromboembolism in mice lacking the prostaglandin E receptor subtvpe EP_3"Circulation. 104. 1176-1180 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Xiao, C.-Y.: "Roles of prostaglandin 12 and thromboxane A2 in cardiac ischemia-reperfusion injury ; a study using mice lacking their respective receptors"Circulation. 104. 2210-2215 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Narumiya, S. et al.: "Prostanoid receptors: structures, properties and functions"Physol. 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] 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] Ushikubi, F. et al.: "Roles of prostanoids revealed from studies using mice lacking -specific prostanoid receptors"Jpn. J. Pharmacol.. 83. 279-285 (2000)

    • 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. Pharmacol.. 131. 745-755 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ma, H. et al.: "Increased bleeding tendency and decreased susceptibility to thromoembolism in mice lacking the prostaglandin E receptor subtype EP_3"Circulation. 104. 1176-1180 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Xiao, C.-Y. et al.: "Roles of prostaglandin I_2 and thromboxane A_2 in cardiac ischemia-reperfusion injury: a study using mice lacking their respective receptors"Circulation. 104. 2210-2215 (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."British Journal of 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."Japan Journal of Pharmacology. 83. 279-285 (2000)

    • 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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