Molecular mechanism of anesthesia of xenon : specific or nonspecific effect?
| Project/Area Number |
10470317
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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 | Osaka University |
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Principal Investigator |
MASHIMO Takashi Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (60157188)
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| Co-Investigator(Kenkyū-buntansha) |
HAMANAKA Toshiaki Osaka University Graduate School of Engineering Science, Assistant Professor, 基研工学研究科, 助手
UCHIDA Ichiro Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (00232843)
NISHIMURA Shinya Osaka University Hospital, Assistant Professor, 医学部・附属病院, 助手 (00263286)
YOSHIYA Ikuto Osaka University Hospital, Professor, 医学部・附属病院, 教授 (80028505)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | anesthetic action / mechanism / specific / non specific / xenon / nitrous oxide / GABA_A recptor / NMDA receptor / キセノン / イソフルラン / セボフルラン / 揮発性麻酔薬 / 重水 / イソフルレン / MAC |
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| Research Abstract |
1) Binding of volatile anesthetics to purple membranes studied by X-ray diffraction.
The concentrated purple membranes suspension was sealed in a 1 mm diameter glass capillary which also included buffer solution with or without volatile anesthetic, diiodomethane at its both sides. The X-ray diffraction pattern was recorded on a imaging plate and read by an image scanner. The X-ray diffraction study showed that anesthetics bound specifically to the protein-lipid interfacial region within a trimer near the surface of bacteriorhodopsin in the purple membrane.
2) Effects of xenon, nitrous oxide and volatile anesthetics on recombinant GABA_A receptors and recombinant NMDA receptors expressing in Xenopusoocyte.
Mouse cDNAs encoding for α1, β2 and γ2s GABA_A receptor subunits, and for ζ1, ε1 NMDA receptor were subcloned into transcription vector. A vector containing each subunit was linearized by an appropriate restriction enzyme to create the template cDNA and cRNA was synthesized in vitro. Different combinations of GABA_A receptor subunits (α1 β2 and α1 β2 γ2s ) and NMDA receptor (ζ1 ε1) were injected to Xenopusoocyte followed by incubation at 20℃ for >48h. The electrophysiological recordings were made by using the two electrode-voltage clamp technique. Volatile anesthetics potentiated GABA-induced current in dose dependent manners in the α1 β2 and α1 β2 γ2s receptors, but xenon and nitrous oxide showed no significant potentiation. On the contrary, volatile anesthetics did not affect NMDA-induced current in the ζ1 ε1 recentor, but xenon and nitrous oxide depressed it dose-dependently.
The results suggest that an inert gas, xenon acts on neuronal receptors in the specific manner.
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Report
(4 results)
Research Products
(8 results)
