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Is an Inhibitor of Histamine-Forming Enzyme a New Type of "Anti-histamine" ?

Research Project

Project/Area Number 61870012
Research Category

Grant-in-Aid for Developmental Scientific Research

Allocation TypeSingle-year Grants
Research Field General pharmacology
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

MAEYAMA Kazutaka (1988)  Tohoku University School of Medicine, 医学部, 助手 (00157158)

渡辺 建彦 (1986-1987)  東北大学, 医学部, 教授 (70028356)

Co-Investigator(Kenkyū-buntansha) 長田 久美子  兵庫医科大学, 助手 (90068502)
YAMATODANI Atsushi  Osaka University Medical School, 医学部, 助教授 (30116123)
MATSUNAGA Tohru  Osaka University Medical School, 医学部, 教授 (10101271)
ONODERA Kenji  Tohoku University School of Dentistry, 歯学部, 助手 (40133988)
WATANABE Takehiko  Tohoku University School of Medicine, 医学部, 教授 (70028356)
KAWAGUCHI-NAGATA Kumiko  Hyogo Medical College
八木 忍  自治医学大学, 講師 (10111296)
前山 一隆  東北大学, 医学部, 助手 (00157158)
Project Period (FY) 1986 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥21,000,000 (Direct Cost: ¥21,000,000)
Fiscal Year 1988: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1987: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1986: ¥13,000,000 (Direct Cost: ¥13,000,000)
KeywordsHistamine / Histidine decarboxylase / alpha-Fluoromethylhistidine / Suicide substrate / Histamine depletion / Peptic ulcer / Motion sickness / 動揺病 / ヒスタミン受容体 / αーフルオロメチルヒスチジン / α-フルオロメチルヒスチジン
Research Abstract

a-Fluoromethylhistidine (FMH) is a specific inhibitor of L-histidine decarboxylase (HDC), a histamine-forming enzyme. The purpose of this study is as follows (1) Is histamine depletion caused by administration of FMH effective as drugs for pathological conditions for which histamine is responsible? (2) Does the histamine depletion evoke serious side effects, beacause histamine plays roles in various physiological states? In terms of (1), FMH strogly inhibited the histamine production in gastric carcinoid of Mastomys natalensis and completely protected peptic ulcer formation caused by excess acid production. Also FMH inhibited a pica reaction, a kaolin intake response after double rotation stimutation in rats, which is a model of motion sickness. In terms of (2), histamine depletion caused by long-term administration of FMH in guinea-pigs did not change the sensitivity of histamine H_1 and H_2 receptors, as judged by the insignificant changes in [3H]-mepyramine binding and cAMP producti … More on as chemical markers, and contractions of the ileum and atrium as physiological responses, respectively. in screening test of general pharmacology of FMN in mice and rats, no significan effects were observed except in higher doses (greater than 100 mg/kg). On closer examination of its effect on CNS, however, FMH affected a little in the circadian rhythms of plasma concentrations of corticosteron and ACTH or sleep-awakeness, and retarded the phase of free-run rhythms of spontaneous and drinking behaviors. FMH also did not affect the regulation of immune responses like antibody formation and contact sensitivity reaction in the skin caused by dinitrophenylfluorobenzene in guinea-pigs. The pharmacokinetical analysis showed that FMH administered i.v. was not easily transported into the brain, stomach and liver, but rapildy rapidly excreted from the kidney, giving the basis for future studies. To sum up, the possiblity was demonstrated that FMH might be useful as a drug f or pep-tic ulcer or motion sickness and histamine depletion did not cause serious side effects, although further studies will be required. Less

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Shun Hosoda: Biochemical Pharmacology. 34. 4327-4329 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 大和谷厚: 病態生理. 5. 660-667 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Noriaki Takeda: Acta Otolaryngologia. 101. 416-421 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 武田憲昭: 神経精神薬理. 9. 559-566 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Fukuda: Agents and Actions. 24. 56-64 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hisayoshi Niigawa: Brain Research. 459. 183-186 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Masahiro Morita: Otorhinolaryngology. 50. 188-192 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Masahiro Morita: Otorhinolaryngology. 50. 330-333 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Kumiko Kawaguchi-Nagata: Biochimica Biophysica Acta. 972. 249-256 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Ruriko Mamune: Journal Allergy and Clinical Immunology. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Nobuko Itowi: Neuroendocrinology. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Kenji Onodera: Tohoku Journal of Experimental Medicine. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 渡邉建彦: "神経内分泌 2.生理活性物質" 中外医学社, 16 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Noriaki Takeda: "Bical Sciences in Space 1986" MYU Research, 5 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 渡邉建彦: "蕁麻疹皮膚科MOOK 12" 金原出版, 12 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Takehiko Watanabe: "Handbook of Experimental Pharmacology:Histamine and Histamine Antagonists." Springer, 20 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Shun,Hosoda: "Marked inhibition of histamine formation in transplantable histamine-producing gastric carcinoid of Mastomys natalensis by (S)-alpha-fluoro-methylhistidine and its potent antiulcer effect on tumor-bearing hosts." Biochemical Pharmacology. 34. 4327-4329 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Noriaki,Takeda: "Histaminergic mechanisms of motion sickness; neurochemical and neuropharmacological studies of rats." Acta Otolaryngologia. 101. 416-421 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi,Fukuda: "Long-term depletion of histamine in guinea-pigs by administration of alpha-fluoromthylhistidine, a specific inhibitor of histidine decarboxylase; Effect on the sensitivity of histamine receptors." Agents and Actions. 24. 56-64 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hisayoshi,Niigawa: "Effect of neurotoxic lesions in the mammillary bodies on the distri-bution of brain histamine." Brain Research. 459. 183-186 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Masahiro,Morita: "Pica as an index of motion sickness of rats." Otorhinolaryngology. 50. 188-192 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Masahiro,Morita: "Effects of anti-motion sickness drugs on motion sickness in rats." Otorhinolaryngology. 50. 330-333 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Kumiko,Nagata-Kawaguchi: "Increase of histidine decarboxylase activity in murine myelocytic leukemia cells (WEHI-3B) in parallel to their defferentiation into macrophages." Biochimica Biophysica Acta. 972. 249-256 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Ruriko,Mamune: "Histidine decarboxylase in human basophilic leukemia (KU-812F) cells; Characterization and induction by phorbolmyristate acetate." Journal of Allergy and Clinical Immunology. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Nobuko,Itowi: "Effect of histamine depletion on circadian variations of corticotropin and corticosterone in rats." Neuropharmacology. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Kenji,Onodera: "Effects of alpha-fluoromethylhistidine on locomotor activity in rats." Tohoku Journal of Experimental Pharmacology. (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Noriaki,TAkeda: Bical Sciences in Space 1986. MYU Research, 173-177 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Takehiko,Watanabe: Handbook of Experimental Pharmacology; Histamine and Histamine Antagonists.Springer, 20 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Hiroshi Fukuda: Agents and Actions. 24. 56-64 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Masahiro Morita: Otorhinolaryngology. 50. 330-333 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Kumiko Kawaguchi-Nagata: Biochimica Biophysica Acta. 972. 249-256 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Ruriko Mamune: Journal of Allergy and Clinical Immunology. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Nobuko Itowi: Neuroendocrinology. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Kenji Onodera: Tohoku Journal of Experimental Medicine. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 渡邊建彦: "蕁麻疹,皮膚科MOOK12" 金原出版, 190-201 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Takehiko Watanabe: "Handbook of Experimental Pharmacology:Histamine and Histamine Antagonists." Springer, 20 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Shun Hosada: Biochemical Pharmacology. 34. 4329-4331 (1985)

    • Related Report
      1986 Annual Research Report
  • [Publications] Noriaki Takeda: Acta Otolaryngologia(Stockholm). 101. 416-421 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Nobuko Itowi: Japanese Jounal of Pharmacology. 40(Suppl). 155 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 渡邉建彦: 臨床科学. 22. 1097-1103 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 大和谷厚: 病態生理. 5. 660-667 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Hiroshi Fukuda: British Journal of Pharmacology.

    • Related Report
      1986 Annual Research Report
  • [Publications] 渡辺建彦(矢内厚昇編): "ヒスタミン 神経内分泌 2 生理活性物質" 中外医学社, 231-246 (1986)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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