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Development study of preventive and therapeutic drugs for Alzheimertype senile dementia by using biologically active peptides

Research Project

Project/Area Number 07672396
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionMeijo University

Principal Investigator

UKAI Makoto  Ph.D., Associate Professor Department of Chemical Pharmacology Faculty of Pharmaceutical Sciences Meijo University, 薬学部, 助教授 (80131209)

Co-Investigator(Kenkyū-buntansha) KAMEYAMA Tsutomu  Ph.D., Professor Department of Chemical Pharmacology Faculty of Pharmaceutical S, 薬学部, 教授 (10076698)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsBiologically active peptides / Alzheimer's disease / Deltorphin / Galanin / Passive avoidance learning / Opioids / Tachykinins / Spontaneous alternation performance / ダイノルフィン / サブスタンスP / ニューロキニンA / 生物活性ペプチド / 記憶
Research Abstract

1. Effects of substance P on scopolamine-induced impairment of spontaneous alternation performance
(1) Substance P improved the scopolamine-induced impairment of spontaneous alternation performance.
(2) The improving effects of substance P were antagonized by treatment with the tachykinin NK-1 receptor antagonist WIN62577.
2. Effects of Tyr-D-Arg-Phe-beta-Ala-NH_2 (TAPA) on passive avoidance learning
(1) TAPA inhibited passive avoidance learning.
(2) The impairing effects of TAPA were reversed by treatment with mu-opioid receptor antagonist beta-funaltrexamine.
3. Effects of galanin on passive avoidance learning, elevated plus-maze learning and spontaneous alternation performance
(1) Galanin inhibited passive avoidance learning, although it had no effects on elevated plusmaze learning or spontaneous alternation performance.
4. Effects of systemic administration of dynorphin A-(1-13) on cycloheximide-induced impairment of passive avoidance learning
(1) The intraperitoneal injection of dynorphin A-(1-13) impaired the cycloheximide-induced impairment of passive avoidance learning.
(2) The improving effects of dynorphin A-(1-13) were reversed by treatment with the kappa-opioid receptor antagonist nor-binaltorphimine.
5. Effects of delta-opioid receptor agonists on learning and memory
(1) [D-Pen^2, L-Pen^5] enkephalin and [D-Ala^2] deltorphin II inhibited passive avoidance learning, although they did not affect spontaneous alternation performance or elevated plus-maze learning.
These results suggest that opioid peptides selective for mu-and delta-opioid receptors and galanin evoke anmesia, while substance P and dynorphin possess anti-amnesic effects. Moreover, it is possible that dynorphin is one of the nootropic neuropeptides.

Report

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

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Makoto Ukai: "Substance P markedly ameliorates scopolamine-induced impairment of spontaneous alternation performance in the mouse." Brain Research. 673. 335-338 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Ukai: "Attenuation of memory with Tyr-D-Arg-Phe-β-Ala-NH_2,a novel dermorphin analog with high affinity for μ-opioid receptors." European Journal of Pharmacology. 287. 245-249 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Ukai: "Effects of galanin on passive avoidance response,elevated plus-maze learning,and spontaneous alternation performance in mice." Peptids. 16. 1283-12 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Ukai: "Neurokinin A and senktide attenuate scopolamine-induced impairment of spontaneous alternation performance in mice." Japanese Journal of Psychopharmacology. 16. 97-101 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Ukai: "Systemic administration of dynorphin A-(1-13) markedly improves cycloheximide-induced amnesia in mice." European Journal of Pharmacology. 313. 11-15 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Ukai: "Effects of the k-opioid dynorphin A-(1-13) on learning and memory in mice." Behavioral Brain Research. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Ukai, Norihiro Shinkai, Kayoko Ohashi and Tsutomu Kameyama: "Substance P markedly ameliorates scopolamine-induced impairment of spontaneous alternation performance in the mouse." Brain Research. 673. 335-338 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Ukai, Tetsuya Kobayashi, Kaori Mori, Norihiro Shinkai, Yusuke Sasaki and Tsutomu Kameyama: "Attenuation of memory with Tyr-D-Arg-Phe-beta-Ala-NH_2, a novel dermorphin analog with high affinity for mu-opioid receptors." European Journal of Pharmacology. 287. 245-249 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Ukai, Masataka Miura and Tsutomu Kameyama: "Effects of galanin on passive avoidance response, elevated plus-maze learning, and spontaneous alternation performance in mice." Peptides. 16. 1283-1286 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] MAkoto Ukai, Norihiro Shinkai and Tsutomu Kameyama: "Neurokinin A and senktide attenuate scopolamine-induced impairment of spontaneous alternation performance in mice." Japanese Journal of Psychopharmacology. 16. 97-101 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Ukai, X.Shan-Wu, Tetsuya Kobayashi and Tsutomu Kameyama: "Systemic administration of dynorphin A-(1-13) markedly improves cycloheximide-induced amnesia in mice." European Journal of Pharmacology. 313. 11-15 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Ukai: "Substance P markedly ameliorates scopolamine-induced impairment of spontaneous alternation performance in the mouse." Brain Research. 673. 335-338 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Makoto Ukai: "Attenuation of memory with Tyr-D-Arg-Phe-β-Ala-NH_2, a novel dermorphin analog with high affinity for μ-opioid receptors." European Journal of Pharmacology. 287. 245-249 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Makoto Ukai: "Effects of galanin on passive avoidance response, elevated plus-maze learning and spontaneous alternation performance in mice." Peptides. 16. 1283-1286 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Makoto Ukai: "Neurokinin A and senktide attenuate scopolamine-induced impairment of spontaneous alternation performance in mice." Japanese Journal of Psychopharmacology. 16. 97-101 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Makoto Ukai: "Systemic administration of aynorphin A-(1-13) markedly improves cycloheximide-induced amnesia in mice." European Journal of Pharmacology. 313. 11-15 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M. Ukai, N. Shinkai, K. Ohashi and T. Kameyama: "Substance P markedly ameliorates scopolamine-induced impairment of spontaneous alternation performance in the mouse" Brain Res.673. 335-338 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M. Ukai, N. Shinkai and T. Kameyama: "κ-Opioid receptor agonists improve pirenzepine-induced disturbance of spontaneous alternation performance in the mouse" Eur. J. Pharmacol.281. 173-178 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] M. Ukai, M. Miura and T. Kameyama: "Effects of galanin on passive avoidance response, elevated plus-maze learning, and spontaneous alternation performance in mice" Peptides. 16. 1283-1286 (1995)

    • Related Report
      1995 Annual Research Report

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

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