| Project/Area Number |
15390479
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | University of Occupational Environmental Health(UOEH) |
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Principal Investigator |
SHIGEMATSU Akio UOEH, President, 学長 (30037428)
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| Co-Investigator(Kenkyū-buntansha) |
MINAMI Kouichiro UOEH, School of medicine, assistant professor, 医学部, 講師 (70279347)
UEZONO Yasuhito Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬総合研究科, 助教授 (20213340)
UETA Yoichi UOEH, School of medicine, professor, 医学部, 教授 (10232745)
HORISHITA Takahumi UOEH, School of medicine, instructor, 医学部, 助手 (40369070)
SHIRAISHI Minehiro UOEH, School of medicine, instructor, 医学部, 助手 (40389458)
尾方 純一 産業医科大学, 医学部, 助手 (50352331)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2005: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2004: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2003: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Anesthetics / dorsal root ganglia cells / ion channels / G-protein coupled receptor (GPCR) / Xenopus oocyte / substance P / Tramadol / orexin A / 電位依存性Naチャネル / ステロイド系静脈麻酔薬アルファキサロン / 静脈麻酔薬 / イソフルラン / エンフルラン / エーテル / ハロセン / 疼痛発生メカニズム / イオンチャンネル / G蛋白結合受容体 |
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| Research Abstract |
The effects of anesthetics on ion channels have been the focus of several studies. During the last decade, major advances have been made in our understanding of the physiology and pharmacology of G-protein coupled receptor (GPCR) signaling. Further studies have shown that GPCRs are targets for anesthetics. However, less is known about the mechanisms of action of anesthetics on GPCRs, ion channels and ligand-gated ion channels in spinal cords levels. The Xenopus oocyte expression system has been used widely to study numerous brain ion channels and GPCRs. A large number of types have been found on primary afferent neurons, either on their central or peripheral processes or on the cell bodies of the dorsal root ganglion (DRG) cells and it is have been reported the presence of several GPCRs. Therefore the DRG have been used for the study of nociception.
(1)We studied the effects of anesthetics on substance P-evoked intracellular [Ca^<2+>] ([Ca^<2+>]_i)increasing in cultured DRG cells. Substance P induced a rapid [Ca^<2+>]_i increase in single DRG cell. Volatile anesthetics halothane inhibited the substance P-evoked increases in [Ca^<2+>]_i.
(2)Tramadol, metabolite M1 and alphaxalone inhibited voltage dependent Na channels expressed in Xenopus oocytes that expressed M_3. High concentration of dexmedetomidine inhibited voltage dependent Na channels expressed in Xenopus oocytes that expressed M_3.
(3)Most volatile anesthetics inhibited substance P receptor function expressed in Xenopus oocytes that expressed M_3. Moreover, ketamine and pentobarbital inhibited substance P receptor function expressed in Xenopus oocytes that expressed M_3.
(4)We studied the effects of anesthetics on orexin A and neuropeptide FF-evoked [Ca^<2+>]_i increasing in cultured DRG cells. Orexin A and neuropeptide FF induced a rapid [Ca^<2+>]_i increase in single DRG cell suggesting that these receptors exist in DRG.
Our present results would be useful for understanding the mechanisms of anesthetics.
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