| Project/Area Number |
13671627
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE |
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Principal Investigator |
HAZATO Tadahiko THE TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, MEDICAL R&D CENTER, PRINCIPAL SCIENTIST, 東京都臨床医学総合研究所, 副参事研究員 (60109949)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Kinya JUNTENDO UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部・麻酔学教室, 助教授 (80164581)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Spinorphin / Enkephalin / Spinal Cord / Pain / Opioid / DPPIII / オピオイド / enkephain |
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| Research Abstract |
We found a novel endogenous inhibitor that modulated enkephalin activity and purified it from spinal cord based on its inhibitory activity toward enkephalin-degrading enzymes. Structural analysis revealed the factor to be L-V-V-Y-P-W-T and it was named spinophrin. It inhibits dipeptidyl peptidaseIII(EC3.4.14.4:DPPIII) as well as aminopeptidase(EC3.4.1:AP), neutral endopeptidase(EC3.4.24.11: NEP), angiotensin-converting enzyme (EC3.4.15.1:ACE) from monkey brain, especially to DPPIII(Ki: 5.1x10-7). Spinorphin also inhibited polymorphonuclear neutrophil(PMN) function by suppressing FMLP binding to its receptor on PMNs. Recently we reported that this inhibitor against DPP111 significantly inhibited bradykinin-induced responses. It showed analgesia in a different manner compared with morphine. Its analgesia may be caused by an inhibitory activity toward enkephalin-degrading enzyme, DPPIII. It would be interesting to determine whether spinorphin or more active related compounds inhibit neuropathic pain, known to be insensitive to morphine. Spinorphin plays important roles in pain and further search of its analogues may lead to finding of a novel type of drugs which will be useful for various clinical application
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