| Project/Area Number |
10671874
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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 |
Surgical dentistry
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| Research Institution | Osaka University |
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Principal Investigator |
MATSUMOTO Ken Osaka University, Faculty of Dentistry, Associate Professor, 歯学部, 助教授 (20127301)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUYAMA Hiromichi Osaka University, Dental Hospital, Senior Resident, 歯学部・附属病院, 医員
ATSUMI Yukako Osaka University, Dental Hospital, Senior Resident, 歯学部・附属病院, 医員
IKUZAWA Misao Osaka University, Dental Hospital, Senior Resident, 歯学部・附属病院, 医員
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | morphine / tolerance / calcium channel / ω-conotoxin GVIA / clonidine / peroxynitrite / cell death / scavenging / ω-conotoxinGVIA / N型カルシウムチャネル / P,Q型カルシウムチャネル |
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| Research Abstract |
We demonstrated in this study that calcium channels, especially N-type, in brain cortex increased not only the quantity but the functional calcium influx on morphine tolerant stage. Analgesic effect of intracerebroventricular administration of ψ-conotoxin (ψ-CTx) GVIA, an N-type voltage-sensitive calcium channel blocker, in morphine-or clonidine-tolerant mice was examined. The effects of ψ-CTx GVIA and other ψ-toxins (ψ-agatoxin IV A and ψ-CTx MVILA) on 45Ca uptake into synaptosomes prepared from brain cortex of these tolerant mice were also examined. In both tolerant mice, the analgesic effect of ψ-CTx GVIA was significantly decreased, and K+-stimulated 45Ca uptake into these cortical synaptosomes significantly increased, compared with control mice. 45Ca uptake into the synaptosomes of control mice was reduced by not only ψ-CTx GVIA but also other_-toxins, and the inhibition of 45Ca uptake by these toxins was attenuated in both tolerant mice. These results suggest that N-type calcium channels play some important roles for antinotiception, and are concerned with the development of morphine or clonidine tolerance through the increase of presynaptic calcium influx as well as the upregulation of opioid receptor.
We also examined the interaction between morphine and nitric oxide (NO). Peroxynitrite induced cell death accompanied by DNA fragmentation in human neuroblastoma SH-SY5Y cell cultures. Morphine prevented the cell death induced by peroxynitrite. The protective effect of morphine was concentration-dependent, but was not antagonized by naloxone. The selective ligands for opioid receptor subtypes did not prevent the cell death induced by peroxynitrite. Tease results suggest that morphine prevent peroxynitrite-induced cell damage through its direct scavenging action.
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