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NEW DEVELOPMENT OF PHARMACOLOGICAL RESEARCH FOR HISTAMINE : USING MAST CELL DEFICIENT RAT

Research Project

Project/Area Number 07557011
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field General pharmacology
Research InstitutionEHIME UNIVERSITY

Principal Investigator

MAEYAMA Kazutaka  EHIME UNIVERSITY,MEDICINE,PROFESSOR, 医学部, 教授 (00157158)

Co-Investigator(Kenkyū-buntansha) ADACHI Naoto  EHIME UNIVERSITY,MEDICINE,ASSISTANT, 医学部・附属病院, 助手 (50253315)
MOCHIZUKI Takatoshi  EHIME UNIVERSITY,MEDICINE,ASSISTANT, 医学部, 助手 (40263933)
GOTOH Yoshinori  EHIME UNIVERSITY,MEDICINE,LECTURER, 医学部, 講師 (10162166)
YAMATODANI Atsushi  OSAKA UNIVERSITY,MEDICINE,PROFESSOR, 医学部, 教授 (30116123)
WATANABE Takehiko  TOHOKU UNIVERSITY,MEDICINE,PROFESSOR, 医学部, 教授 (70028356)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1995: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsMAST CELLS / HISTAMINE / N^<tau>-METHYLHISTAMINE / IN VIVO MICRODIALYSIS / GASTRIC SECRETION / RESTRAINT STRESS / PAW EDEMA / MAST CELL DEFICIENT RATS / N^t-メチルヒスタミン / 炎症 / N^7N-メチルヒスタミン / ヒスタミン・ニューロン
Research Abstract

In this research project, using mast cell deficient (Ws/Ws) rats, roles of histamine in the pathophysiological conditions such as allergy, gastric ulcer and behavior have been investigated. There are at least two types of histamine pools : one is mast cell-histamine and another is nin-mast cell histamine. As mast cells contain high amount of histamine and are distributed widely, it was difficult to differentiate these two histamine pools. Ws/Ws rats, which has a mutation of c-kit receptor, completely deplete connective tissue type of mast cells. Therefore, histamine contents in tissues of Ws/Ws rats derive from non-mast cell histamine. We can clearly demonstrate the existence of non-mast cell histamine and its roles as follows.
1.Histamine content in the brain of Ws/Ws rats is 63% of the congenic (+/+) rats and it decreased to 37% of the control level after treatment of alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase. The remaining content of histamine might … More be due to other pool than mast cells and neuron. (J.Neurochem.65 : 791,1995)
2.Using in vivo microdialysis technique, the relationship between edema formation and histamine release in the paw was studied. After treatment of compound 48/80, histamine release sharply occurs in 20 min and decreased gradually through 3 hrs in +/+ rats but no edema formation and histamine release was observed in Ws/Ws rats. Compound 48/80 stimulates histamine release from mast cells and edema formation. (Eur.J.Pharmacol.331 : 237,1997)
3.In water immesion stress, plasma histamine levels increased biphasically in normal rats. In the first phase, it reached a peak at 15 min and the second increase was observed between 1.5-6 hrs. After gastrectomy, the second increasein plasma histamine disappeared. In Ws/Ws rats, the water immersion stress causes no first peak and aftr gastrectomy, both increases in plasma histamine disappeared. Non-immunological stimulant causes histamine release from mast cells after water immersion stress. Less

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Sugimoto, K.: "Brain histaminergic system in mast cell-deficient(Ws/Ws)rats:histamine content,histidine decarboxylase activity,and effects of (S)α-fluoromethylhistidine" J.Neurochem.65. 791-797 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Alam, M.K.: "Simultaneous determination of histamine and N^τ-methylhistamine by high-performance liquid chromatography-chemiluminescence coupled with immobilized diamine oxidase" Anal.Biochem.229. 26-34 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Goto, Y.: "The release and subsequent synthesis of histamine in a transfected subclone of rat basophilic leukemia cells that expresses human muscarinic m1 receptors" Jpn.J.Pharmacol.69. 167-171 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe, H.: "Transient increase of blood histamine level induced by pentagastrin:Continuous monitoring by in vivo microdialysis" Scand J Gastroenterol. 31. 1144-1150 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mochizuki, T.: "Brain penetration of the histamine H3 receptor antagonists thioperamide and clobenpropit in rat and mouse,determined with ex vivo [^<125>I]iodophenpropit binding" Brain Res.743. 178-183 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Guo, Y.: "Role of mast cell histamine in the formation of rat paw edema:a microdialysis study" Eur.J.Pharmacol.331. 237-243 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugimoto, K.et al.: "Brain histaminergic system in mast cell-deficient (Ws/Ws) rats : histamine content, histidine decarboxylase activity, and effects of (S) alpha-fluoromethylhistidine" J.Neurochem.65. 791-797 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Alam, M.K.et al.: "Simultaneous determination of histamine and N^<tau>-methylhistamine by high- performance liquid chromatography-chemilumminescence coupled with immobilized diamine oxidase" Anal.Biochem.229. 26-34 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Goto, Y.et al.: "The release and subsequent synthesis of histamine in a transfected subclone of rat basophilic leukemia cells that expresses human muscarinic m1 receptors" Jpn.J.Pharmacol.69. 167-171 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Watanabe, H.et al.: "Transient increase of blood histamine level induced by pentagastrin Continuous monitoring by in vivo microdialysis" Scand J Gastroenterol. 31. 1144-1150 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mochizuki, T.et al.: "Brain penetration of the histamine H3 receptor antagonists thioperamide and clobenpropit in rat and mouse, determined with ex vivo [^<125>I] iodophenpropit binding" Brain Res.743. 178-183 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Guo, Y.et al.: "Role of mast cell histamine in the formation of rat paw edema : a microdialysis study" Eur.J.Pharmacol.331. 237-243 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Guo Y.: "Role of mast cell histamine in the formation of rat paw edema:a microdialysis study" Eur. J. Pharmacol.331. 237-243 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe H.: "Transient increase of blood histamine level induced by pentagastrin." Scand.J.Gastroenterol. 31. 1144-1150 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kim C-Y: "The brain histamine (HA) and pituitary luteinzing hormone (LH) levels in female rats anesthetized with ether on proestrus." Exp.Anim.45(2). 175-177 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Guo Y.: "Role of mast cell histamine in formation of rat paw edema." Eur.J.Pharmac.(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sugimoto K.: "Effects of α-fluoromethyl- (S) -histidine on the histamine content and histidine decarboxylase activity in the different regions of the brain of mast cell-defficient (Ws/Ws) rats." J.Neuronchem.65. 791-797 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Alam M.K.: "Simultaneous determinations of histamine and N^τ-methylhistamine by high-performance liquid chromatography-chemiluminescence coupled with immobilized diamine oxidase." Anal.Biochem.229. 26-34 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Okayama M.: "Localization of histamine N-methyltransferase messenger RNA in human nasal mucosa." J.Allerg.Clin.Immunol.95. 96-102 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Goto Y.: "Insulin-like action of chromate on glucose transport in isolated rat adipocytes." Jpn.J.Pharmacol.67. 365-368 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Goto Y.: "The release and subsequent synthesis of histamine in a transfected subclone of rat basophilic leukemia cells that expresses human muscarinic ml receptors." Jpn.J.Pharmacol.69. 167-171 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sakurai E.: "Effects of the histamine H3 agonist (R) -α-methylhistamine and the antagonist thioperamide in vitro on monoamine oxidase activity in the rat brain." Methods and Findings. 17 Suppl.C.46-50 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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