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2002 Fiscal Year Final Research Report Summary

ANGIOGENIC INHIBITION OF SPINORPHIN , A POTENT ANALGESIC AND ANTIINFLAMMATORY SUBSTANCE

Research Project

Project/Area Number 13672410
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

SHIMAMURA Marko  THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, MEDICAL R&D CENTER, RESEARCHER, 東京都臨床医学総合研究所, 主任研究員 (00124462)

Co-Investigator(Kenkyū-buntansha) HAZATO Tadahiko  THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, MEDICAL R&D CENTER, RESEARCHER, 東京都臨床医学総合研究所, 副参事研究員 (60109949)
Project Period (FY) 2001 – 2002
Keywordsangiogenesis / spinorphin / analgesia / CAM / endothelial cells / enkephalin / enzyme inhibitor / bradykinin
Research Abstract

Angiogenesis is the formation of new blood vessels and is essential for tissue development, regeneration and remodeling. Angiogenesis also plays an important role in many pathological processes, such as growth and metastasis of solid tumor, diabetic retinopathy, rheumatoid arthritis and psoriasis. The inhibition of angiogenesis results in suppression of these diseases. On the other hand, we previously found a small peptide with inhibiting activity against proteases that degraded endogenous opioid peptide, enkephalin in human spinal fluid and purified it named as spinorphin from bovine spinal cord. Spinorphin is a peptide that consists seven amino acid residues, LVVYPWT. Spinorphin potently inhibited enkephalin-degrading enzymes and exhibited analgesic activity in mice and inflammatory responses such as chemotaxis, O_2-generation and exocytosis by human polymorphonuclear nutrophils.
In this study, we investigated the antiangiogenic activity of spinorphin using in vivo and in vitro assays … More . First we examined its antiangiogenic activity using a chick embryo chorioallantoic membrane (CAM). Spinorphin potently inhibited angiogenesis, dose-dependently. This activity increased by simultaneous addition of an aminopeptidase inhibitor, leuhistin since spinorphin was degraded by aminopeptidase in CAM assay. The mechanism of this inhibition was examined using endothelial cells. This compound did not inhibit proliferation or tube formation of bovine pulmonary artcrial endothelial (BPAE)cells. Previously, spinorphin was reported to inhibit bradykinin-induced nociceptive flexor responses in mice. This suggested that spinorphin may bind bradykinin receptors. We examined antiangiogenic activity of bradykinin antagonists and they showed potent inhibition of angiogenesis in CAM. However, spinorphin did not inhibit binding of bradykinin to bradykinin receptors. Moreover, a specific receptor for spinorphin was suggested to exist in rat spinal cord. In contrast, some inhibitors of angiotensin-converting enzyme (ACE) or aminopeptidase (AP) suppressed angiogenesis in CAM. As spinorphin inhibits enzyme activities of ACE and AP, antiangiogenic activity of spinorphin may depend on its enzyme regulation. Less

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Shimamura, M et al.: "Inhibition of angiogenesis by humulone, a bitter acid from beer hop"Biochem.Biophys.Res.Commun.. 289. 220-224 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kasai, s et al.: "Design and synthesis of antiangiogenic/heparin-binding arginine dendrimer mimicking the surface of cndostatin"Bioorg.Med.Chem.Lett.. 12. 951-954 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagasawa, H et al.: "Design, synthesis and biological activities of antangiogenic hypoxic cytotoxin, triazine-N-oxide derivatoves"Comp.Biochem.Physiol.A Mol.Integr.Physiol.. 132. 33-40 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hazato, T. et al.: "A new pain regulated substance spinorphin from spinal cord"Jpn.J.Pharmacol. 86. 138 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimamura, M. et al.: "A hypoxia-dependent nitroimidazole KIN-841 inhibits tumor-specific angiogenesis by blocking production of angiogenic factors"Brit.J.Cancer. 88. 307-313 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamamoto, Y. et al.: "Spinorphin as an Endogenous Inhibitor of Enkepjalin-degrading Enzymes : Roles in Pain and Inflammation"Current Protein and Peptide Sciences. 587-599 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 羽里 忠彦: "食肉に関する助成研究調査成果報告書,伊藤記念財団"ウシ脊髄由来の新しい生理活性物質・Spinorphinの研究. 4 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shimamura, M., Hazato, T., Ashino, H., Yamamoto, Y., Iwasaki, E. ,Tobe, H., Yamamoto, K., Yamamoto, S.: "Inhibition of angiogenesis by humulone, a bitert acid from beer hop"Biochem. Biophys. Res. Commun.. 289. 220-224 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kasai, S., Nagasawa, H., Shimamura, M., Uto, Y. and Hori, H.: "Design and synthesis of antiangiogenic/heparin-binding arginine dendrimer mimicking the surface of endostatin"Bioorg.Med. Chem.Lett.. 12. 951-954 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagasawa, H., Yamashita, M., Mikamo, N., Shimamura, M., Oka, S., Uto, Y. and Hori, H.: "Design, synthesis and biological activities of antiangiogenic hypoxic cytotoxin, triazine-N-oxide derivatives"Comp. Biochem. Physiol. A Mol. Integr. Physiol.. 132. 33-40 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hazato, T., Yamamoto, Y., Shimamura, M., Takayama, T., Nishimura, K. and Ueda, H.: "A new pain regulated substance spinorphin from spinal cord"Jpn. J.Pharmacol.. 88, Suppl. 1. 138 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto, Y., Ono, H., Ueda, A., Shimamura, M., Nishimura, K. and Hazato, T.: "Spinorphinas an endogenous inhibitor of enkephalin-degrading enzymes: Roles in pain and inflammation"Current Protein and Peptide Sciences. 3. 587-599 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shimamura, M., Nagasawa, H., Ashino, H., Yamamoto, Y., Hazato, T., Uto, Y., Hori, H. and Inayama, S.: "A hypoxia-dependent nitroimidazole KIN-841 inhibits angiogenesis by blocking production of angiogenic factor"Brit. J. Cancer. 88. 307-313 (2003)

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

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Published: 2004-04-14  

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