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Studies in anti-inflammatory effect of spinorphin, an endogenous factor

Research Project

Project/Area Number 10672168
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionTokyo Metropolitan Organization of Medical Science

Principal Investigator

YAMAMOTO Yukio  Tokyo Metropolitan Institute of Medical Science Researcher, 東京都臨床医学総合研究所, 研究員 (80124501)

Co-Investigator(Kenkyū-buntansha) HAZATO Tadahiko  Tokyo Metropolitan Institute of Medical Science Researcher, 東京都臨床医学総合研究所, 研究員 (60109949)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsspinorphin / an endogenous factor / inflammation / dipeptidyl peptidase
Research Abstract

It has been known that spinorphin has the inhibitory activity toward various enkephalin-degrading enzymes, such as neutral endopeptidase, aminopeptidase and dipeptidyl peptidase III (DPPIII) in central nerve system. In this study, the inhibitory activity toward DPPIII on human PMNs was found using a specific substrate (Arg-Arg-β-naphtylamide) and inhibitors.
To characterize anti-inflammatory effect of spinorphin, an endogenous peptide purified from bovine spinal cord, priming of spinorphin on human neutrophils (PMNs) and quantitative method of spinorphin in human serum were investigates.
(1) Priming effect of superoxide generation by stimulant-induced PMNs
Spinorphin (1μM) alone did not induce superoxide generation. However, by secondary stimulation with FMLP, an inflammatory stimulant, the activity was markedly augmented compared to that of nontreated control. From FACS analysis, expression of CD11b and CD18, adhesion molecules was significantly increased compared with that of control, suggesting that the priming effect of spinorphin is in part due to increase of expression of adhesion molecules.
(2) Effect of apinorphin on dipeptidyl peptidase III enzymatic activity
(3) Quantitative method of spinorphin by ELISA
Anti-spinorphin antibody was produced in rabbits immunized with keyhole limpet hemocyanin (KLH)-conjugated spinorphin. Quantitative method of spinorphin by ELISA was established. Anti-spinorphin antibody did not complete with its analogues in this method. Base levels of spinorphin in human serum were 0.23±0.25 pmol/ml.
From these results, spinorphin may be a peptide regulator in inflammation.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Yukio Yamamoto: "Inhibitory action of spinorphin, an endogenous regulator of enkephalin-dagrading enzymes, on carageenan-induced polymorphonuclear neutrophil accumulation in mouse air-pouches"Life Sciences. 62(19). 1767-1773 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 阿部通: "好中球表層アミノペプターゼNの慢性疼痛患者における動態"麻酔. 47(3). 151-155 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhide Yamaguchi: "Granulocyte colony-stimulating factor-induced dephosphorylation of a 45 kD cytosolic protein in HL-60 cells differentiating into neutrophils"Br. J. Haematol.. 102. 798-803 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yukio Yamamoto: "Characterization of tynorphin, a potent endogenous inhibitor of dipeptidyI peptidaseIII"Peptides. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yukio yamamoto, Tadahiro Kanazawa, Mariko Shimamura, Masaaki Ueki and Tadahiko Hazato: "Inhibitory action of spinorphin, an endogenous regulator of enkephalin-degrading enzymes, on carrageenan-induced polymorphonuclear neutrophil accumulation in mouse air-pouch."Life Sciences. 62. 1767-1773 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Toru Abe, Yukio Yamamoto and Tadahiko Hazato: "Changes in aminopeptidase N on poly-morphonuclear leukocytes derived from patients with chronic patients."Jpn. J. Anethesiol.. 47. 151-155 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Teruhide Yamaguchi, Tadashi Oshizawa, Takamasa Yamaguchi, Kazuhiro Suzuki, Yukio Yamamoto and Takao Hayakawa: "Granulocyte colony-stimulating factor-induced dephosphorylation of a 45 kD cytosolic protein in HL-60 cells differentiating into neutrophils."Br. J. Haematol.. 102. 798-803 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yukio Yamamoto, Jun-ichi Hashimoto, Mariko Shimamura, Teruhide Yamaguchi and Tadahiko Hazato: "Characterization of tynorphin, a potent endogenous inhibitor of dipeptidyl peptidase III."Peptides. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 阿部通: "好中球表面アミノペプダーゼNの慢性疼痛患者における動態"麻酔. 47(2). 151-155 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yukio Yamamoto: "Characterization of tynorphin, a potent endogenous inhibitor of dipeptidyl peptidase III"Peptides. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yukio Yamamoto: "Inhibitory action of spinorphin,an endogenous regulator of enkephalin-degrading enzymes,on carrageenan-induced polymorphonuclear neotrophil accumulation in mouse air-pouches." Life Sciences. 62(19). 1767-1773 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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