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Mechanism of action of a new endogenous antipyretic

Research Project

Project/Area Number 11670068
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionKyoto Institute of Technology

Principal Investigator

NAKASHIMA Toshihiro  Kyoto Inst. of Technology, Guraduate School of Science and Technology, Associate Professor, 工芸科学研究科, 助教授 (30128136)

Co-Investigator(Kenkyū-buntansha) MIYATA Seiji  Kyoto Inst. of Technology, Guraduate School of Science and Technology, Instructor, 工芸科学研究科, 助手 (30243124)
KIYOHARA Toshikazu  Kyoto Inst. of Technology, Faculty of Textile Science, Professor, 繊維学部, 教授 (50071874)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsAntipyresis / Fever / Arachidonic acid cascade / EET / EET
Research Abstract

Fever as a component of a host-defense response is associated with enhanced survival. The current model of fever involves pyrogenic cytokines and the subsequent induction of prostaglandins (PGs) by these cytokines, particularly stimulation of PGE_2. The action of classic antipyretic agents is primarily attributed to the inhibition of cyclooxygenase (COX) of arachidonic acid cascade and subsequently reduced generation of PGs. In addition to COX, it is now known that cytochrome P-450 branch of arachidonic acid cascade. Various inhibitors of cytochrome P-450 augment fever in rats and mice, indicating that the enzyme may be involved in endogenous antipyresis.
Male Wistar rats were implanted with telemetry transmitters in the abdominal cavity to monitor body temperature under anesthesia. In some experiments, rats were implanted with brain cannulas in addition to the telemeters. To determine the site of action of cytochrome P-450 metabolites in the brain, cytochrome P-450 inhibitor (SKF-525A) … More was microinjected into the various site of brain in conscious male rats. SKF-525A was injected 15 min prior to intraperitoneal injection of lipopolysaccharide. Microinjections of SKF-525A into the mPOA, paraventricular nucleus and 3rd ventricle enhanced the LPS-induced fever, while injections into dorsal hypothalamic area, fornix and reticular hypothalamic nucleus showed no remarkable effect on the fever. Second, various isomers of epoxyeicosatrienoic acids (EETs), metabolites of cytochrome P-450, were tested influence on fever. Each EETs were microinjected into the mPOA in conscious rats, 10 min before IL-1β injection using same cannula. 11, 12-EET attenuated fever compared with vehicle treated group. 5, 6-, 8, 9- and 14, 15-EET had no significant antipyretic effect on the time course of fever.
These results suggest that the site of antipyretic action of cytochrome P-450 is antero-medial part of the hypothalamus, and that 11, 12-EET is a candidate of endogenous antipyretic which may be produced in the hypothalamus by endogenous pyrogens. Less

Report

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

    (14 results)

All Other

All Publications (14 results)

  • [Publications] W.Matsunaga: "Microtuble-associated protein-2 in the hypothalami-neurohypophysial system."Neuroscience. 88. 1289-1297 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Ichikawa: "Developmental changes in capacitative Ca^<2+> entry in mouse mammary epithelial cells."Cell Biochem, Funct.. 18. 147-150 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Ichikawa : "EGF enhances Ca^<2+> mobilization and capacitative Ca^<2+> entry in mouse mammary epithelial cells."Cell Biochem. Funct.. 18. 215-225 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] W.Matsunaga : "LPS-induced Fos expression in oxytocin and vasopressin neurons of the rat hypothalamus"Brain Res. . 858. 9-18 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 中島敏博: "脳と体温"共立出版. 212 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] W.MATSUNAGA, S.MIYATA, Y.HASHIMOTO, S.-H.LIN T.NAKASHIMA, T.KIYOHARA and T.MATSUMOTO: "Microtuble-associated protein-2 in the pypothalamo-neurohypophysial system : low-molecular-weight microtuble-associated protein-2 in pituitary astrocytes."Neuroscience. 88. 1289-1297 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.ICHIKAWA, K.FURUYA, S.MIYATA, T.NAKASHIMA and T.KIYOHARA: "Developmental Changes in capacitative Ca^<2+> entry in mouse mammary epithelial cells."Cell Biochem. Funct.. 18. 147-150 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.ICHIKAWA, k.FURUYA, S.MIYATA, T.NAKASHIMA and T.KIYOHARA: "EGF enhances Ca^<2+> mobilization and capacitative Ca^<2+> entry in mouse mammary epithelial cells."Cell Biochem. Funct.. 18. 215-225 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] W.MATSUNAGA, S.MIYATA, A.TAKAMATA, H.BUNN, T.NAKASHIMA and T.KIYOHARA: "LPS-induced Fos expression in oxytocin and vasopressin neurons of the rat hypothalamus."Brain Res.. 858. 9-18 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] J.Ichikawa: "Developmental changes in capacitative Ca^<2+> entry in mouse mammary epithelial cells."Cell Biochem.Funct.. 18. 147-150 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] J.Ichikawa: "EGF enhances Ca^<2+> mobilization and capacitative Ca^<2+> entry in mouse mammary epithelial cells."Cell Biochem.Funct.. 18. 215-225 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] W.Matsunaga: "LPS-induced Fos expression in oxytocin and vasopressin neurons of the rat hypothalamus."Brain Res.. 858. 9-18 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 中島敏博: "脳と体温"共立出版. 212 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] W.Matsunaga: "Microtuble-associated protein-2 in the hypothalamo --"Neuroscience. 88(4). 1289-1297 (1999)

    • Related Report
      1999 Annual Research Report

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

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