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Presynaptic monoacylglycerol lipase activity determines basal endocannabinoid tone and terminates retrograde endocannabinoid signaling in the hippocampus
https://doi.org/10.24517/00013178
https://doi.org/10.24517/0001317844e15e16-8dcc-4ab8-b7a1-bd40a29bc9e1
名前 / ファイル | ライセンス | アクション |
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ME-PR-SHOSAKU-T-1211.pdf (893.5 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-10-03 | |||||
タイトル | ||||||
タイトル | Presynaptic monoacylglycerol lipase activity determines basal endocannabinoid tone and terminates retrograde endocannabinoid signaling in the hippocampus | |||||
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_6501 | |||||
資源タイプ | journal article | |||||
ID登録 | ||||||
ID登録 | 10.24517/00013178 | |||||
ID登録タイプ | JaLC | |||||
著者 |
Hashimotodani, Yuki
× Hashimotodani, Yuki× Ohno-Shosaku, Takako× Kano, Masanobu |
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著者別表示 |
少作, 隆子
× 少作, 隆子× 狩野, 方伸 |
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提供者所属 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 金沢大学大学院医学系研究科機能障害学 | |||||
書誌情報 |
Journal of Neuroscience 巻 27, 号 5, p. 1211-1219, 発行日 2007-01-31 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0270-6474 | |||||
NCID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA10620404 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1523/jneurosci.4159-06.2007 | |||||
出版者 | ||||||
出版者 | Society for Neuroscience | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Endocannabinoids function as retrograde messengers and modulate synaptic transmission through presynaptic cannabinoid CB1 receptors. The magnitude and time course of endocannabinoid signaling are thought to depend on the balance between the production and degradation of endocannabinoids. The major endocannabinoid 2-arachidonoylglycerol (2-AG) is hydrolyzed by monoacylglycerol lipase (MGL), which is shown to be localized at axon terminals. In the present study, we investigated how MGL regulates endocannabinoid signaling and influences synaptic transmission in the hippocampus. We found that MGL inhibitors, methyl arachidonoyl fluorophosphonate and arachidonoyl trifluoromethylketone, caused a gradual suppression of cannabinoid-sensitive IPSCs in cultured hippocampal neurons. This suppression was reversed by blocking CB1 receptors and was attenuated by inhibiting 2-AG synthesis, indicating that MGL scavenges constitutively released 2-AG. We also found that the MGL inhibitors significantly prolonged the suppression of both IPSCs and EPSCs induced by exogenous 2-AG and depolarization-induced suppression of inhibition/excitation, a phenomenon known to be mediated by retrograde endocannabinoid signaling. In contrast, inhibitors of other endocannabinoid hydrolyzing enzymes, fatty acid amide hydrolase and cyclooxygenase-2, had no effect on the 2-AG-induced IPSC suppression. These results strongly suggest that presynaptic MGL not only hydrolyzes 2-AG released from activated postsynaptic neurons but also contributes to degradation of constitutively produced 2-AG and prevention of its accumulation around presynaptic terminals. Thus, the MGL activity determines basal endocannabinoid tone and terminates retrograde endocannabinoid signaling in the hippocampus. Copyright © 2007 Society for Neuroscience. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | This work was supported by Grants-in-Aid for Scientific Research 18-08582 (Y.H.), 17650112, 17024021, and 18022016 (T.O.-S.), and 17023021 and 17100004 (M.K.) from the Ministry of Education, Culture, Sports, Science, and Technology ofJapan. Y.H. is arecipient of Research Fellowships oftheJapan Societyforthe Promotion of Science for Young Scientists. |
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権利 | ||||||
権利情報 | Copyright © Society for Neuroscience | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
関連URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://www.jneurosci.org/content/27/5/1211 | |||||
関連名称 | https://www.jneurosci.org/content/27/5/1211 |