1999 Fiscal Year Final Research Report Summary
Study on the function of endogenous opioid and substance P at inflammation and pain
| Project/Area Number |
10671443
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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 | Juntendo University |
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Principal Investigator |
NISHIMURA Kinya Juntendo University, School of Med., Assistant Professor, 医学部, 講師 (80164581)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Yukio The Tokyo Metropolitan Institute of Medical Science, Chief Researcher, 主任研究員 (80124501)
HAZATO Tadahiko The Tokyo Metropolitan Institute of Medical Science, Chief Researcher, 主任研究員 (60109949)
KUGIMIYA Toyoki Juntendo University, School of Med., Professor, 医学部, 教授 (90010537)
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| Project Period (FY) |
1998 – 1999
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| Keywords | spinorphin / enkephalin / aminopeptidase / bradykinin / Ni-NTA / dipeptydylaminopeptidase / substance P / substance P receptor |
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| Research Abstract |
We synthesized spinorphin analogous and assayed their inhibitoriy activity toward dipeptidyl peptidase III (DPPIII) among enkephalin degrading enzymes. VVYPW, an N-terminal and C-terminal truncated form of spinorphin, exhibited more potent inhibitory activity.
This results indicated that VVYPW had amore effective structure of expression of inhibitory activity toward DPPIII.
We attempted to characterize nociceptive sensory fibers into three types, and examined the mode of action of spinorphin-induced analgesia, in comparison to morphine-induced one.
So, spinorphin completely blocked 2-metyl-thioadenosine induced responsed, but morphine did not. On the other hand, morphine-induced blockade of bradykinin responses was attenuated by pertussis toxin treatment, while the spinorphin's ones was not. Thus it is suggested that spinorphin has wide spectrum of analgesia which covers the blockade of nociception insensitive to morphine.
Regarding to purification of human substance P receptor, we have developed a recombinant Substance P receptor with 6xHis epitope at its N-terminus. The 6xHis tag does not interfere with receptor's ability to bind ligands the 6XHis-SPR can be purified over the Ni-NTA column. This purification procedure constitutes an important step toward obtaining large quantities of homogeneous SPR for structural studies.
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