○種別 (必須): | □ | 学術論文 (審査論文)
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○言語 (必須): | □ | 英語
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○招待 (推奨): |
○審査 (推奨): | □ | Peer Review
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○学究種別 (推奨): |
○組織 (推奨): | 1. | 徳島大学.医学部.医学科.病態情報医学講座
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| 2. | 徳島大学.医学部.医科栄養学科.特殊栄養学講座 (〜2004年3月31日/->組織[徳島大学.医学部.医科栄養学科.臨床実践栄養学講座.代謝栄養学])
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○著者 (必須): | 1. | 河野 崇
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| 2. | 大下 修造
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| 3. | 髙橋 章 ([徳島大学.大学院医歯薬学研究部.医学域.栄養科学部門.医科栄養学系.予防環境栄養学])
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| 4. | 堤 保夫
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| 5. | 富山 芳信 ([徳島大学.病院.中央診療施設等.手術部])
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| 6. | 北畑 洋
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| 7. | 黒田 泰弘
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| 8. | 中屋 豊
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○題名 (必須): | □ | (英) Molecular mechanisms of the inhibitory effects of propofol and thiamylal on sarcolemmal adenosine triphosphate-sensitive potassium channels. (日)
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○副題 (任意): |
○要約 (任意): | □ | (英) Both propofol and thiamylal inhibit adenosine triphosphate-sensitive potassium (KATP) channels. In the current study, the authors investigated the effects of these anesthetics on the activity of recombinant sarcolemmal KATP channels encoded by inwardly rectifying potassium channel (Kir6.1 or Kir6.2) genes and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) genes. The authors used inside-out patch clamp configurations to investigate the effects of propofol and thiamylal on the activity of recombinant KATP channels using COS-7 cells transfected with various types of KATP channel subunits. Propofol inhibited the activities of the SUR1/Kir6.2 (EC50 = 77 microm), SUR2A/Kir6.2 (EC50 = 72 microm), and SUR2B/Kir6.2 (EC50 = 71 microm) channels but had no significant effects on the SUR2B/Kir6.1 channels. Propofol inhibited the truncated isoform of Kir6.2 (Kir6.2DeltaC36) channels (EC50 = 78 microm) that can form functional KATP channels in the absence of SUR molecules. Furthermore, the authors identified two distinct mutations R31E (arginine residue at position 31 to glutamic acid) and K185Q (lysine residue at position 185 to glutamine) of the Kir6.2DeltaC36 channel that significantly reduce the inhibition of propofol. In contrast, thiamylal inhibited the SUR1/Kir6.2 (EC50 = 541 microm), SUR2A/Kir6.2 (EC50 = 248 microm), SUR2B/Kir6.2 (EC50 = 183 microm), SUR2B/Kir6.1 (EC50 = 170 microm), and Kir6.2DeltaC36 channels (EC50 = 719 microm). None of the mutants significantly affects the sensitivity of thiamylal. These results suggest that the major effects of both propofol and thiamylal on KATP channel activity are mediated via the Kir6.2 subunit. Site-directed mutagenesis study suggests that propofol and thiamylal may influence Kir6.2 activity by different molecular mechanisms; in thiamylal, the SUR subunit seems to modulate anesthetic sensitivity. (日)
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○キーワード (推奨): | 1. | (英) ATP-Binding Cassette Transporters (日) (読)
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| 2. | (英) Anesthetics, Intravenous (日) (読)
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| 3. | (英) Animals (日) (読)
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| 4. | (英) Cells, Cultured (日) (読)
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| 5. | (英) Diazoxide (日) (読)
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| 6. | (英) Electrophysiology (日) (読)
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| 7. | (英) Glyburide (日) (読)
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| 8. | (英) Humans (日) (読)
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| 9. | (英) Molecular Biology (日) (読)
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| 10. | (英) Patch-Clamp Techniques (日) (読)
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| 11. | (英) Pinacidil (日) (読)
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| 12. | (英) Potassium Channels (日) (読)
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| 13. | (英) Potassium Channels, Inwardly Rectifying (日) (読)
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| 14. | (英) Propofol (日) (読)
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| 15. | (英) Rats (日) (読)
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| 16. | (英) Receptors, Drug (日) (読)
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| 17. | (英) Thiamylal (日) (読)
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| 18. | (英) Vasodilator Agents (日) (読)
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○発行所 (推奨): |
○誌名 (必須): | □ | Anesthesiology ([The American Society of Anesthesiologists])
(pISSN: 0003-3022, eISSN: 1528-1175)
○ISSN (任意): | □ | 0003-3022
ISSN: 0003-3022
(pISSN: 0003-3022, eISSN: 1528-1175) Title: AnesthesiologyTitle(ISO): AnesthesiologyPublisher: Lippincott Williams & Wilkins Ltd. (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login])
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○巻 (必須): | □ | 100
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○号 (必須): | □ | 2
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○頁 (必須): | □ | 338 346
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○都市 (任意): |
○年月日 (必須): | □ | 西暦 2004年 2月 初日 (平成 16年 2月 初日)
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○URL (任意): |
○DOI (任意): | □ | 10.1097/00000542-200402000-00024 (→Scopusで検索)
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○PMID (任意): | □ | 14739809 (→Scopusで検索)
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○備考 (任意): | 1. | (英) Article.Affiliation: Department of Anesthesiology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. haf26740@ams.odn.ne.jp (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't (日)
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