Looking for the role of cannabinoid receptor heteromers in striatal function.
Looking for the role of cannabinoid receptor heteromers in striatal function.
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DOI：
10.1016/j.neuropharm.2008.06.076
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发表时间：
2009
影响因子：
4.7
通讯作者：
Franco R
中科院分区：
文献类型：
--
作者：
Ferré S;Goldberg SR;Lluis C;Franco R
“局部模块”和“受体异构体”这两个概念的引入，有助于理解大脑中不同神经递质之间相互作用的作用。在人工细胞系统中，大麻素CB1受体与多巴胺D2、腺苷A2a和μ阿片受体形成受体异构体。有间接但令人信服的证据表明，在以纹状体GABA能传出神经元的树突为中心的纹状体局部模块中存在相同的CB1受体异构体，特别是在突触后位置。他们的分析为内源性大麻素在纹状体功能中的作用提供了新的线索，纹状体功能不能只被认为是抑制神经递质释放的逆行信号。最近的研究表明，CB1、D2和A2A受体可以在转基因细胞中形成异三聚体，这是一种检测两种以上蛋白质异构化的新方法。在GABA能脑啡肽能神经元的树突棘中，可能可以发现功能性CB1-A2A-D2受体异构体，在它们高度共表达的地方。这些多受体异构体的功能特性以及它们在纹状体功能中的作用需要确定。
The introduction of two concepts, “local module” and “receptor heteromer”, facilitates the understanding of the role of interactions between different neurotransmitters in the brain. In artificial cell systems, cannabinoid CB1 receptors form receptor heteromers with dopamine D2, adenosine A2A and μ opioid receptors. There is indirect but compelling evidence for the existence of the same CB1 receptor heteromers in striatal local modules centered in the dendritic spines of striatal GABAergic efferent neurons, particularly at a postsynaptic location. Their analysis provides new clues for the role of endocannabinoids in striatal function, which cannot only be considered as retrograde signals that inhibit neurotransmitter release. Recent studies using a new method to detect heteromerization of more than two proteins, which consists of sequential BRET-FRET (SRET) analysis, has demonstrated that CB1, D2 and A2A receptors can form heterotrimers in transfected cells. It is likely that functional CB1-A2A-D2 receptor heteromers can be found where they are highly co-expressed, in the dendritic spines of GABAergic enkephalinergic neurons. The functional properties of these multiple receptor heteromers and their role in striatal function need to be determined.
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