Mode of action and physiological significance of endogenous cannabinoids as a retrograde messenger at central synapses
内源性大麻素作为中央突触逆行信使的作用模式和生理意义
基本信息
- 批准号:13854028
- 负责人:
- 金额:$ 66.89万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (S)
- 财政年份:2001
- 资助国家:日本
- 起止时间:2001 至 2004
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The active component of marijuana (Δ^9-tetrahydrocannabinol) exerts various psychomotor actions through binding to the CB1 cannabinoid receptor that is distributed widely in the central nervous system. Two candidates for endogenous cannabinoid (eCB) (i.e.,endogenous ligands for the CB1 receptor) are anandamide and 2-arachidonoylglycerol. The CB1 receptor is present at presynaptic sites of central neurons and the binding of cannabinoids to this receptor results in reduction of neurotransmitter release from presynaptic terminals. However, at the beginning of the present research project, it was largely unknown what stimuli to neurons could produce eCBs and what roles eCBs played in brain functions. We have examined roles of eCBs in modulation of synaptic transmission by using electrophysiological methods and have obtained the following results.In hippocampal neurons and cerebellar Purkinje cells, depolarization and resultant elevation of intracellular Ca^<2+> concentration causes production of eCBs that retrogradely activates presynapric CB1 receptors and induces transient suppression of neurotransmitter release. Activation of Gq-coupled receptors including group I metabotropic glutamate receptors and M_1/M_3 muscarinic acetylcholine receptors also induces eCB-mediated rretrograde suppression of neurotransmitter release. Furthermore, we have found that, in cutured hippocampal neurons, weak depolarization and mild activation of M_1/M_3 muscarinic acetylcholine receptors effectively induce eCB-mediated retrograde suppression, whereas either stimulus alone causes no detectable suppression. We have disclosed that this synergism is attributable to the property of phospholipase Css1 (PLCss1) that is activated by a subunit of Gq/11 and also sensitive to physiological range of intracellular Ca^<2+>. Therefore, PLCss1 can function as a coincidence detector of cholinergic afferent activity (i.e.,presynaptic activity) and postsynaptic depolarization.
大麻的活性成分(Δ^9-四氢大麻酚)通过与广泛分布于中枢神经系统的CB1大麻素受体结合,发挥各种精神运动作用。内源性大麻素 (eCB)(即 CB1 受体的内源性配体)的两种候选物是 anandamide 和 2-arachidonoylglycerol。 CB1 受体存在于中枢神经元的突触前位点,大麻素与该受体的结合会导致突触前末梢释放的神经递质减少。然而,在本研究项目开始时,人们基本上不知道什么刺激神经元可以产生 eCB 以及 eCB 在大脑功能中发挥什么作用。我们使用电生理学方法研究了 eCB 在突触传递调节中的作用,并获得了以下结果。在海马神经元和小脑浦肯野细胞中,去极化和由此导致的细胞内 Ca^2+ 浓度升高导致 eCB 的产生,逆行激活突触前 CB1 受体并诱导神经递质释放的短暂抑制。 Gq偶联受体(包括I组代谢型谷氨酸受体和M_1/M_3毒蕈碱乙酰胆碱受体)的激活也会诱导eCB介导的神经递质释放的逆行抑制。此外,我们发现,在剪切的海马神经元中,M_1/M_3 毒蕈碱乙酰胆碱受体的弱去极化和轻度激活有效诱导 eCB 介导的逆行抑制,而单独的刺激不会引起可检测到的抑制。我们已经公开,这种协同作用归因于磷脂酶Css1(PLCss1)的特性,其被Gq/11的亚基激活并且还对细胞内Ca 2+ 的生理范围敏感。因此,PLCss1 可以充当胆碱能传入活动(即突触前活动)和突触后去极化的重合检测器。
项目成果
期刊论文数量(114)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
ORP150/HSP12A regulates Purkinje cell survival : A role for ER stress in cerebellar development.
ORP150/HSP12A 调节浦肯野细胞存活:内质网应激在小脑发育中的作用。
- DOI:
- 发表时间:2004
- 期刊:
- 影响因子:0
- 作者:Kitao;Y.
- 通讯作者:Y.
T. Ohno, Shosaku: "Cooperative endocannabinoid production by neuronal depolarization and group I metabotropic glutamate receptor activation"Eur. J. Neurosci.. (in press). (2002)
T. Ohno, Shosaku:“神经元去极化和 I 类代谢型谷氨酸受体激活协同产生内源性大麻素”Eur。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Fukudome, Y.: "Insulin-like growth factor-I as a promoting factor for cerebellar Purkinje cell development"Eur.J.Neurosci.. 17. 2006-2016 (2003)
Fukudome, Y.:“胰岛素样生长因子-I 作为小脑浦肯野细胞发育的促进因子”Eur.J.Neurosci.. 17. 2006-2016 (2003)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
mGluR1 in cerebellar Purkinje cells is required for normal association of temporally contiguous stimuli in classical conditioning
- DOI:10.1046/j.1460-9568.2002.02407.x
- 发表时间:2002-12-01
- 期刊:
- 影响因子:3.4
- 作者:Kishimoto, Y;Fujimichi, R;Kirino, Y
- 通讯作者:Kirino, Y
狩野方伸: "内因性カンナビノイドによる逆行性シナプス伝達 学術月報"日本学術振興会. 5 (2003)
Masanobu Kano:“内源性大麻素的逆行突触传递。科学月报”日本科学促进会 5 (2003)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
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KANO Masanobu其他文献
KANO Masanobu的其他文献
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{{ truncateString('KANO Masanobu', 18)}}的其他基金
Advanced Bioimaging Support
先进的生物成像支持
- 批准号:
16H06280 - 财政年份:2016
- 资助金额:
$ 66.89万 - 项目类别:
Grant-in-Aid for Scientific Research on Innovative Areas ― Platforms for Advanced Technologies and Research Resources
Targeted gene expression in single neurons by opto-poration in vivo
通过体内光穿孔在单个神经元中靶向基因表达
- 批准号:
23650204 - 财政年份:2011
- 资助金额:
$ 66.89万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Studies on activity-dependent maturation of synaptic function during postnatal cerebellar development
出生后小脑发育过程中突触功能活动依赖性成熟的研究
- 批准号:
17023021 - 财政年份:2005
- 资助金额:
$ 66.89万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
Elucidation of neural network function in the brain
阐明大脑中的神经网络功能
- 批准号:
16069101 - 财政年份:2004
- 资助金额:
$ 66.89万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
Molecular Mechanisms for Activity-dependent Elimination of Supernumerary Excitatory Synapses in Developing Cerebellum
发育中小脑中多余兴奋性突触活动依赖性消除的分子机制
- 批准号:
10480230 - 财政年份:1998
- 资助金额:
$ 66.89万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Moleculare Mechanisms of Synapse Elimination and Stabilization in Developing Brain
大脑发育过程中突触消除和稳定的分子机制
- 批准号:
08458264 - 财政年份:1996
- 资助金额:
$ 66.89万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Identification of signal transduction cascades involved in long-lasting potentiation of inhibitory synapses
鉴定参与抑制性突触持久增强的信号转导级联
- 批准号:
05454677 - 财政年份:1993
- 资助金额:
$ 66.89万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
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以辣椒素受体为靶点抗肝纤维化作用的研究
- 批准号:81071716
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- 资助金额:10.0 万元
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- 批准号:30870803
- 批准年份:2008
- 资助金额:38.0 万元
- 项目类别:面上项目
相似海外基金
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TRPV1 通道在海马突触传递和可塑性中的作用
- 批准号:
8005220 - 财政年份:2010
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$ 66.89万 - 项目类别:
Role of TRPV1 channels in synaptic transmission and plasticity in the hippocampus
TRPV1 通道在海马突触传递和可塑性中的作用
- 批准号:
8098896 - 财政年份:2010
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$ 66.89万 - 项目类别:
Cannabinoid Modulation of Cortical Synaptic Transmission
大麻素对皮质突触传递的调节
- 批准号:
7059442 - 财政年份:2003
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$ 66.89万 - 项目类别:
Cannabinoid Modulation of Cortical Synaptic Transmission
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- 批准号:
7225484 - 财政年份:2003
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$ 66.89万 - 项目类别:
Cannabinoid Modulation of Cortical Synaptic Transmission
大麻素对皮质突触传递的调节
- 批准号:
6785459 - 财政年份:2003
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$ 66.89万 - 项目类别:
Cannabinoid Modulation of Cortical Synaptic Transmission
大麻素对皮质突触传递的调节
- 批准号:
6878950 - 财政年份:2003
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$ 66.89万 - 项目类别:
Cannabinoid Modulation of Cortical Synaptic Transmission
大麻素对皮质突触传递的调节
- 批准号:
6677522 - 财政年份:2003
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$ 66.89万 - 项目类别:
Physiological roles of plasticity of inhibitory synaptic transmission
抑制性突触传递可塑性的生理作用
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13680899 - 财政年份:2001
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$ 66.89万 - 项目类别:
Grant-in-Aid for Scientific Research (C)