| Project/Area Number |
01570100
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Gifu University |
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Principal Investigator |
TSURUMI Kaito Gifu Univ. Sch. of Med. Dept. of Pharmacology, Professor, 医学部, 教授 (60021359)
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| Co-Investigator(Kenkyū-buntansha) |
NOSE Takasi Gifu Univ. Sch. of Med. Dept. of Pharmacology, Research Fellow, 医学部, 助手 (90180744)
NIWA Masayuki Gifu Univ. Sch. of Med. Dept. of Pharmacology, Research Fellow, 医学部, 助手 (40156146)
NOZAKI Masakatsu Gifu Univ. Sch. of Med. Dept. of Pharmacology, Asist. Professor, 医学部, 助教授 (30021380)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1990: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1989: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Polymorphonuclear leukocyte / Superoxide generation / Chemiluminessence / Intracellular calcium movement / Opioid receptor / Kappa opioid / Formyl peptide / Inositol response / 遅発性神経細胞脱落 / 遅発性神経壊死 |
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| Research Abstract |
It has been reported that some opioids modify development of luminol-dependent chemiluminessence (CL)in polymorphonuclear leukocytes (PMNs). PMNs have opioid receptor (s) on the cell surface, but their types and functions are still uncertain. The effects of opioid on CL-development (superoxide generation) and intracellular Ca^<2+>-movement induced by formyl-Met-Leu-Phe (f-MLP) were evaluated in rat peritoneal PMNs.
1.Generation of superoxides : The CL was measured using MCLA. The MCLA-dependent CL stimulated by f-MLP developed in a biphasic manner, resulting in two peaks. A kappa-opioid agonist, U-50488H, enhanced the second peak accelerating O^<2-> generation, and inhibited both CL peaks at 200muM. In contrast, U-50488H dose-dependently inhibited the CL development induced by zymosane or phorbol ester.
2. Intracellular free Ca^<2+>-movements : U-50488H showed little inhibition against Ca^<2+>,-ionophore induced Ca^<2+>-influx. When using f-MLP as a stimulant, U-50488H suppressed both of Ca^<2+>-release from intra-cellular Ca^<2+>-pool and Ca^<2+>-influx from extracelular medium. In this case, the inhibition of the release was more clearly demonstrated. These results were summarized that U-50488H enhanced the superoxide generation at the concentration suppressing the elevation of the intracellular Ca^<2+>-level. Since all of the effects of U-50488H on the CL ant the Ca^<2+>-movements were not antagonized by naloxone, it is supposed that these conflicting effects of the kappa-opioid are not associated with opioid receptor mechanism. The effect of U-50488H was suspected to be caused by selective inhibition of Ca^<2+> store sites by affecting post-receptor mechanisms of f-MLP such as IP_3 response.
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