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Biochemical and Pharmacological Research on Affective Disorders from the Aspect of the Mechanism of Neural Transmission and Intracellural Signal Transduction

Research Project

Project/Area Number 63304044
Research Category

Grant-in-Aid for Co-operative Research (A)

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionGunma University Scholl of Medicine (1989-1990)
Saitama Medical University (1988)

Principal Investigator

HIGUCHI Teruhiko  Gunma University School of Medicine, Associate Prof., 医学部, 助教授 (90105883)

Co-Investigator(Kenkyū-buntansha) SHIBUYA Haruo  Tokyo Medical and Dental University Faculty of Medicene, Lecturer, 医学部, 講師 (10158959)
KOYAMA Tsukasa  Hokkaido University School of Medicene, Associate Prof., 医学部, 助教授 (10113557)
NOMURA Soichiro  Fujita-Gakuen Health University, Associate Prof., 医学部, 助教授 (80113091)
ASAKURA Mikio  St. Marianna University School of Medicine, Associate Prof., 医学部, 助教授 (70103504)
MIKUNI Masahiko  National Institute of Neurosciences, Ncnp,, 神経センター神経研究所, 室長 (00125353)
加藤 進昌  滋賀医科大学, 医学部, 助教授 (10106213)
山脇 成人  国立呉病院,臨床研究部, 室長
Project Period (FY) 1988 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 1990: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1989: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1988: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsAffective Disorders / Antidepressants / Signal Transduction / Neural Transmission / Serotonin / Catecholamine / Second Messenger / ジグナル伝達 / GTP結合 / イノシト-ルリン脂質代謝 / セロトニン受容体 / β受容体 / GABA受容体 / イミプラミン結合 / 細胞内情報伝達 / 神経伝達機構 / 細胞内情報伝達系 / アドレナリン受容体 / アミノ酸受容体
Research Abstract

The remarkable results in this project are as follows.
1. Antidepressants act directly on the second messenger system of 5HT_2 receptor and the direct action on the GTP binding proteins is considered to be important for the mode of action of antidepressants.
2. Protein kinase C (phospholipid-independent/Ca^<++>-dependent kinase) in rat brain membrane was increased by the chronic treatment with antidepressants. This result indicates that antidepressants may keep the continuous activation of PKC.
3. Ca^<++> response with 5HT in the platelets was investigated in the patients with major depression compared to normal controls. Ca^<++> response was much greater in the patients with major depression than in the controls. This result will support the serotonergic supersensitive theory of depression.
4. Chronic treatment of antidepressants causes enhanced coupling of Gs to adenylate cyclase as well as exerting influence on the interaction of Gs and Gi/o.
The classic monoamine hypothesis of depression in which affective disorders are associated with the decrease of NE or 5HT release has been revised in these few years. Recently, the great advances have clarified the second messenger systems and the new direction to study the action for the antidepressants has been shown. In this research project, we found the direct action of antidepressants on the second messenger systems. In addition, in clinical investigation, we found the increased response of second messenger systems in the patients with major depression. Taken together, we present hypothesis that the functional abnormality may exist in the second messenger systems in affective disorders and the action of antidepressants may normalize this abnormality.

Report

(4 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • 1988 Annual Research Report

Research Products

(45 results)

All Other

All Publications (45 results)

  • [Publications] 山脇 成人: "ラット5ーHT_2受容体刺激によるイノシト-ルリン脂質代謝回転に及ぼす躁うつ病治療薬の効果" 精神神経薬理. 12. 33-41 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nakagawara,M.: "The effect of plenylethanolamine ーNー methyltranoferase inhisifor on locomotor activity in rats:The role of central alpha_2ーadreno ceptor and PNMT activity." Neuropsychopharmacology. 227-285 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 小澤 寛樹: "三環系抗うつ剤・電気けいれんショックによるGTP結合蛋白質ーアデニレ-トシクラ-ゼ失役機構に対する影響" 薬物・精神・行動. 10. 21 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yamaoka,K.: "Direct influence of antidepressants on GTP binding protein of adenylate cyclase in cell membranes of the cerebal cortex of rats." J.Neural Transmission. 71. 165-175 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kanba,S.: "Potenticaion by a sodium channel activator of lithium ion effects on cyclic AMP,cyclic GAP and inositol phoophates." Neuropharmacology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Asakura,M.: "Involnement of protein kinass in the regulation of betaーadreneegic receptors by antidepressants." Int.J.Clinical pharmacol.Res.9(2). 123-130 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hayashida,M.: "Solubilizatin and pertial purification of ^3Hーimipramine binding sites from the nat brain." The Japanese Journal of Psychiaty and Neurology. 44. 26-27 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 加藤 進昌: "ソマトスタチンの分子内分泌学" 日本臨床. 47. 2165-2171 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ebisawa,T.: "Toxic effect of desipramine on betaーadrenegic receptors in C_6 glioma cells." Neuropharmacology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] "Proceedings for the 7th workshop for the Biochemical and Pharmacolozical Research on Affective Disorders." The Japanese Journal of Psychiaty and Neurology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 高橋 良: "躁うつ病の生化学(2)ー神経ぺプチドと神経内気泌研究ー" 蛋白質・核酸・酵素. 33. 1300-1306 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Mikuni,M.: "Increased 5ーHTー2 recepton function as measured by serotoninーstimulated phosphoinsitide hydrolysis in platelets of depressed patients." Progress in NeuroーPsychopharnacology & Biologicol Psychiatry. 15. 49-61 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Nagayma,H.: "Animal Study on the Role of Serotonin in Depnession." Clin.Neuropharmacol. 13. 13-14 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kakigi,T.: "The effect of various antidepressants on the concentration of somatostatin in the not brain.(Proceeding)" Jpn.J.Psychiat.Neurol. 44. 145 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Koyama,T.: "Serotorergie and dopaminergic neural change,including receptor changes,after chronic lithium." Clin.Neuropharmacol. 13. 205-206 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kusumi,I.: "Serotoninーstimulated Ca^<2+> response is increased in the blood platelets of depreseed paients." Biol.Psychiat.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 朝倉 幹雄: "躁うつ病 ー基礎と臨床ー 躁うつ病におけるカテコ-ルアミン" 朝倉書店,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 三国 雅彦: "セロトニン受容体機能とうつ病 感情障害ー基礎と臨床ー" 朝倉書店,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 高橋 清久,樋口 輝彦・加藤 進昌・三国 雅彦編: "躁うつ病の薬理生化学[1]" 金剛出版, 166 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 高橋 清久・樋口 輝彦・加藤 進昌・三国 雅彦編: "躁うつ病の薬理生化学[2]" 金剛出版,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 山脇 成人: "ラット5HT_2受容体刺激によるイノシト-ルリン脂質代謝回転に及ぼす躁うつ病治療薬の効果" 精神神経薬理. 12. 33-41 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nakagawara,M.: "The effect of phenylethanolamineーNーmethyltransferase inhibitor on locomotor activity in rats:The role of central α_2ーadrenoceptor and PNMT activity." Neuro psychopharmacology. 277-285 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kanba,S.: "Potentiation by a sodium channel activator of lithium ion effects on cyclic AMP,cyclic GMP and inositol phosphatis." Neuro pharmacology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Mikuni,M.: "Increased 5ーHTー2 receptor function as measured by serotoninーstimulated phospho inositide hydrolysis in platelets of depressed patients." Progress in NeuroーPsychopharmacology & Biological Psychiatry. 15. 49-61 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Nagayama,H.: "Animal Study on the Role of Serotonin in Depression." Clin.Neuropharmacol. 13. 13-14 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kakigi,T.: "The effect of various antidepressants on the concentration of somatostatin in the rat brain (proceeding)" Jpn.J.Psychiat.Neurol.44. 145 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Koyama,T.: "Serotonergic and dopaminergic neural change,including receptor changes,after chronic lithium." Clin.Neuropharmacol.13. 205-206 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kusumi,I.: "Serotoninーstimulated Ca^<2+> response is increased in the blood platelets of depressed patients." Biol.Psychiat.

    • Related Report
      1990 Annual Research Report
  • [Publications] Hayashida,M.: "Solubilization and partial purification of ^3Hーimipramine binding sites from the rat brain." The Japanese Journal of Psychiatry and Neurology. 44. 26-27 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] "Proceedings for the 7th Workshop for the Biochemical and pharmacological Research on Affective Disorders." The Japanese Journal of Psychiatry and Neurology.

    • Related Report
      1990 Annual Research Report
  • [Publications] 高橋 清久・樋口 輝彦・加藤 進昌・三国 雅彦編: "躁うつ病の薬理生化学〔II〕" 金剛出版,

    • Related Report
      1990 Annual Research Report
  • [Publications] "Proceedings for the 5th workshop for the Biochemical and Pharmacological Research on Affective Disorders" The Japanese Journal of Psychiatry and Newrology.

    • Related Report
      1989 Annual Research Report
  • [Publications] 躁うつ病の薬理・生化学的研究懇話会編 編集責任:高橋清久・樋口輝彦・加藤進昌・三国雅彦: "躁うつ病の葉理生化学[I]" 金剛出版, 166 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 海老沢尚: 神経薬基金年報. 20. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 三国雅彦: 神経精神薬理. 10. 521-528 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 土屋文明: 札幌医学雑誌. 58. 15-24 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 本橋伸高: 神経薬療基金年報. 20. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 野村総一郎: 精神薬療基金年報. 20. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 加藤進昌: Life Sciences.

    • Related Report
      1988 Annual Research Report
  • [Publications] 前田潔: Brain Research.

    • Related Report
      1988 Annual Research Report
  • [Publications] 秀和泉: Journal of Neurochemistryt. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] 土山幸之助: 精神薬物行動. 8. 81-82 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 仙波純一: Psychopharmacology. 95. 222-225 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 渋谷治男: 医学のあゆみ. 147. 814-817 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 班員: The Japanese Journal of Psychiatry and Neurology. 42. (1988)

    • Related Report
      1988 Annual Research Report

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Published: 1988-03-31   Modified: 2016-04-21  

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