| Project/Area Number |
16591503
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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 |
Orthopaedic surgery
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| Research Institution | NAGOYA CITY UNIVERSITY |
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Principal Investigator |
FUKUOKA Muneyoshi Nagoya City University, Graduate School of medical Science, research Associate, 大学院・医学研究科, 助手 (80285204)
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| Co-Investigator(Kenkyū-buntansha) |
OHKUBO Iwao Shiga University of medical Science, Professor, 医学部, 教授 (80152073)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Dipeptidyl peptidase III / spinal pain remission system / cerebrospinal fluid / intrinsic opioid / inhibitor(s) |
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| Research Abstract |
1.Interaction between dipeptidyl peptidase III(DPP-III) and its inhibitors
(1)Enzymologic analysis of DPP-III
The cleavage activity of DPP-III, which cleaves dipeptide residues from the amino termini of oligopeptides was measured in cerebraspinal fluid, but not affected with the aminopeptidase in cerebrospinal fluid. We have confirmed to be able to measure the enzymological activity of DPP-III in cerebrospinal fluid of various spinal diseases.
(2)Analysis of inhibitors
Eleven kinds of peptides that have the similar constructions to hemorphin were synthesized. Among them, both peptides IVYPW and WVYPW showed the strongest inhibitory activity to DPP-III. In comparing with IVYPW-NH2 and IVYPW, this newly synthesized peptide IVYPW-NH2 kept enough inhibitory activity to DPP-III. The half-life of IVYPW-NH2 in the blood were 2 times longer than that of IVYPW. According to this result, IVYPW-NH2 may be more useful than IVYPW, regarding as pain remission agent.
There are D-type amino acids in the brain. We changed either of Ile and Val into D type of these synthesized peptides, and then we examined the inhibitory activity of D-Ile and D-Val peptides to DPP-III. The peptide D-Ile showed the strong inhibition to DPP III, but D-Val did not. This result suggested that the most important amino acid for expression of inhibitory activity could be Ile in N-termili. Accordingly, D-IVYPW could be also useful as a pain remission agent.
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