2003 Fiscal Year Final Research Report Summary
Effects of general anesthetics on molecular dynamics and conformation of neuronal receptor channel protains - Molecular mechanism of general anesthesia -
| Project/Area Number |
13470319
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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) |
UCHIDA Ichiro Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (00232843)
SAKO Yasushi Osaka University, Graduate School of Frontier Biosciences, Associate Professor, 生命機能研究科, 助教授 (20215700)
YANAGIDA Toshio Osaka University, Graduate School of Frontier Biosciences, Professor, 生命機能研究科, 教授 (30089883)
西村 信哉 大阪大学, 医学部附属病院, 助手 (00263286)
赤坂 一之 神戸大学, 自然科学研究科, 教授 (50025368)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Anesthesia / Gaseous Anesthetics / volatile anesthetics / GABA_A Receptor / NMDA Receptor / nACh Receptor / 5-HT_3 Receptor / NGF |
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| Research Abstract |
1)Effects of inhalational anesthetics on recombinant GABA_A receptors and NMDA receptors expressed in Xenopus oocyte : Different combinations of GABA_A receptor subunits (α1β2 and α1β2γ2s) and NMDA receptor (ζ1ε1) were injected to Xenopus oocyte followed by incubation at 20℃ for >48h. The electrophystological recordings were made by using the two electrode-voltage champ technique. Volatile anesthetics potentiated GABA-induced current in dose dependent manners in the α1β2 and α1β2γ2s receptors, but xenon (Xe), nitrous oxide (N_2O) showed no significant potentiation. On the contrary, volatile anesthetics did not affect NMDA-induced current in the ζ1ε1 receptor, Xe and N_2O depressed it dose-dependently.
2)Effects of Xe and N_2O on the human neuronal (α_7)_5 nAch receptor expressed in Xenopus oocyte : At clinically relevant concentrations, Xe and N_2O reversibly inhibited the ACh-induced currents of the (α_7)_5 nAch receptor in a concentration-dependent manner. The inhibitory actions of both anesthetics at the (α_7)_5 nAch were non-competitive and voltage-independent.
3)Effects of inhalational anesthetics on human-cloned 5-HT_3 receptor expressed in Xenopus oocyte : Inhalational anesthetics produced deverse effects on the 5-HT_3 receptor. Both halothane and isoflurane enhanced 5-HT_3 receptor function in a concentration-dependent manner. Sevoflurane inhibited the 5-HT-induced current noncopmetitively, whereas Xe and N_2O inhibited the 5-HT_3 receptor competitively. The results suggest that inhalational anesthetics acts on neuronal receptors in the specific manner.
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