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DEXMEDETOMIDINE, A SEDATIVE-ANALGESIC ADJUNCT IN ANESTHESIA, ACTS ON LIPID MEMBRANES: ONE OF POSSIBLE MECHANISMS
https://asahi-u.repo.nii.ac.jp/records/7259
https://asahi-u.repo.nii.ac.jp/records/7259e92ef255-c25a-49e8-b0ab-d08a23d7352b
| Item type | 朝日大学 教育・研究業績(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-10-12 | |||||
| タイトル | ||||||
| タイトル | DEXMEDETOMIDINE, A SEDATIVE-ANALGESIC ADJUNCT IN ANESTHESIA, ACTS ON LIPID MEMBRANES: ONE OF POSSIBLE MECHANISMS | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_1843 | |||||
| 資源タイプ | other | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 業績分類 | ||||||
| 値 | 学会発表 | |||||
| 教員氏名 |
土屋, 博紀
× 土屋, 博紀 |
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| 発行、発表雑誌等、又は発表学会等の名称 | ||||||
| 値 | IARS 2015 Annual Meeting and International Science Symposium (Honolulu, Hawaii) | |||||
| 単著、共著の別 | ||||||
| 値 | 共同発表 | |||||
| 発行又は発表の年月 | ||||||
| 日付 | 2015-03-22 | |||||
| 概要 | ||||||
| 値 | Dexmedetomidine (an S-enantiomer of medetomidine), a highly selective α2 agonist with sympatholytic, sedative and analgesic properties, has been used as an adjunct in regional and general anesthesia. We studied whether it could mechanistically act on lipid membranes as a novel target besides α2 adrenergic and imidazoline receptors. We also characterized its membrane activity by comparing with reference drugs including its antipode, lower selective α2 agonist and anesthetics. Fluorescent probe-labelled lipid bilayer membranes were prepared with 1,2-dipalmitoylphosphatidylcholine to be typical DPPC model membranes and with phospholipids and cholesterol to mimic the membrane lipid compositions of peripheral nerves, central nerves and cardiomyocytes. The membrane preparations were subjected to the reaction with dexmedetomidine, levomedetomidine (R-enantiomeric medetomidine), clonidine, lidocaine, bupivacaine and propofol at 0.01–1 mmol l–1. Their potencies to act on lipid membranes were evaluated by drug-induced membrane fluidity changes that were determined by measuring fluorescence polarization. Dexmedetomidine acted on DPPC model membranes and increased their fluidity as well as reference membrane-acting drugs at 0.01–1 mmol l–1, although its membrane effects were more potent than clonidine, lidocaine and bupivacaine. The comparisons of different fluorescent probes to selectively locate at a graded series of levels in lipid bilayers indicated that dexmedetomidine was more effective at the deeper regions of membranes rather than at the superficial regions. In peripheral nerve-mimetic membranes, the relative potency to increase membrane fluidity was dexmedetomidine > bupivacaine > clonidine > lidocaine at 0.2 mmol l–1 for each (P < 0.05 vs. control for all). In central nerve-mimetic membranes and cardiomyocyte-mimetic membranes, however, dexmedetomidine was less active than propofol at 0.05 mmol l–1. Dexmedetomidine enantio-selectively acted on peripheral nerve-mimetic membranes containing chiral cholesterol much more potently than levomedetomidine at 0.01–0.1 mmol l–1 to induce a 1.6–4 fold increase in membrane fluidity. Dexmedetomidine is able to not only bind to α2 adrenergic and imidazoline receptors but also interact with membrane lipids. Its membrane action is considered to modify the physicochemical property of lipid membranes, thereby directly affecting the functions of biomembranes and indirectly modulating the activities of receptors through the conformational alteration of transmembrane proteins. | |||||
