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1987 Fiscal Year Final Research Report Summary

Studies on the anti-amnesic effect of specific inhibitors for prolyl endopeptidase.

Research Project

Project/Area Number 61571054
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionNagasaki University, School of Pharmaceutical Sciences

Principal Investigator

YOSHIMOTO Tadashi  School of Pharmaceutical Sciences, Nagasaki University, 薬学部, 助教授 (60088870)

Project Period (FY) 1986 – 1987
KeywordsAnti-amnesic effect / Prolyl endopeptidase / Vasopressin / Post-proline cleaving enzyme / Z-Pro-prolinal / インヒビター / プロリルエンドペプチダーゼ
Research Abstract

Several peptides and peptide derivatives were tested for their inhibitory effect on prolyl endopeptidase and possible properties as anti-amnesic agents. Among the compounds tested, Z-Thiopro-thiazolidine, Z-Thiopro-prolinal, Z-Thiopro-thioprolinal inhibited the enzyme activities at Ki values in the order of nM to pM, and the effect of these peptide derivatives was specific for prolyl endopeptidase. Z-Thiopro-thioprolinal was the most effective inhibitor in vitro (Ki=0.005 nM) and in vivo (50 to 70 % inhibition in various organs of rat at a dose of 1 umol/animal i.p.). Regional differences were observed in the effect of inhibitors on the brain enzyme activities: most active in mesencephalon, followed by striatum, cerebellum, hippocampus, hypothalamus; and inactive in cerebral cortex and medulla oblongata. In the passive avoidance learning test using rats, pretreatment with Z-Thiopro-thioprolinal and Z-Pro-prolinal prevented the induction of amnesia by scopolamine at the dose of 1 umol/animal, i.p. Z-Thiopro-thiazolidine, Z-Val-prolinal, Z-Pyr-prolinal and Z-Gly-Pro-CH Cl were also effective in the retention test at 24 and 48 h after the training trial. The anti-amnesic effect of these compounds was approximately parallel to the in vitro inhibitory activities on prolyl endopeptidase. These results suggest the possibility that the inhibitors exhibit their anti-amnesic effect through the regulation of the enzyme activity in the brain.

  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] T.Yoshimoto: J.Pharmacobio-Dyn.10. 730-735 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Yoshimoto: Biochim.Biophys.Acta. 916. 29-37 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Yoshimoto: Agric.Biol.Chem.52. 217-225 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Yoshimoto: Bull.Chem.Pharm.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Yoshimoto: J.Biochem.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Yoshimoto: Agric.Biol.Chem.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Yoshimot: "Specific inhibitors for prolyl endopeptidase and their antiamnesic effect" J. Pharmacobio-Dyn.10. 730-735 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Yoshimoto: "Studies on prolyl endopeptidase from carrot: purification and enzymati properties" Biochim. Biophys. Acta. 916. 29-37 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Yoshimoto: "An aminopeptidase N from Escherichia coli HB101: purification and demonstration that the enzyme possesses arylamidase and peptidase activities." Agric. Biol. Chem.52. 217-225 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Yoshimoto: "Prolyl endopeptidase from bovine testis" Bull. Chem. Pharm.in press.

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Yoshimoto: "Cloning and expression of subtilisin Amylosacchariticus" J. Biochem.in press.

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1989-03-30  

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