| Project/Area Number |
11307027
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Gifu University |
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Principal Investigator |
DOHI Shuji Gifu University School of Medicine, Department of Anesthesiology and Critical Care Medicine, Professor, 医学部, 教授 (40155627)
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| Co-Investigator(Kenkyū-buntansha) |
ODA Akiyoshi Gifu University School of Medicine, Department of Anesthesiology and Critical Care Medicine, Instructor, 医学部・附属病院, 助手 (90273135)
IIDA Hiroki Gifu University School of Medicine, Department of Anesthesiology and Critical Care Medicine, Associate Professor, 医学部, 助教授 (30159561)
辻藤 達也 岐阜大学, 医学部・附属病院, 助手 (10293573)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥21,270,000 (Direct Cost: ¥20,100,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2001: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2000: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1999: ¥11,800,000 (Direct Cost: ¥11,800,000)
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| Keywords | signaling molecules / ion transporter / Na^+-K^+ATPase inhibitor / Na^+-K^+-2Cl^- / Na^+ channels / local anesthetics / lidocaine / apotosis / PLD / PKC / PC12細胞 / 疼痛シグナル / ERK / α_2-アドレナリン / K^+ATPチャネル / イオンチャネル / MAPK / ロピバカイン / シグナル伝達 / TTX / Na^+チャネル / Na^+-K^+-ATPase |
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| Research Abstract |
Although there have been many studies in which local anesthetic action has been examined on Na^+ channels and K^+ channels and Ca^(2+) channels, it has not been known as to roles of ion transporters such as Na^+-K^+ATPase ( Na pump ), Na^+-H^+ exchanger, Na^+-K^+-2CL cotranspoter on anesthetic action as well as pain signal transmission. Using cultured cell lines of PC12 cells and animal model with spinal catheter, we found that since their inhibitors administered into spinal subarachinoid caused significant antinociceptive action, Na^+-K^+ATPase ( Na pump ) and Na^+-H^+ exchanger would have significantrole in local anestheticaction at the spinal cord level, but not with Na^+-K^+-2CL cotranspoter. Oubabain and amiloride seem not to affect signaling molecules such as mitogen-activated protein kinase ( MAPK ) family members, extracellularsignal-regulatedkinases ( ERKs ), PKC, and PLC.
On the other hand, local anesthetics affect such signaling molecules. Local anesthetic tetracaine induces apoptosis of PC12 cells via phosphorylation of MAPK family. ERK activation protects cells from death, but JNK plays the opposite role. Toxic Ca^<2+> influx caused by tetracaine seems to be responsible for apoptoticcell death, but blocking of Na^+ channels and L-type Ca^<2+> channels is unlikely involved in such tetracaine'saction on signaling molecules for apoptosis.
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