Good news for CB1 receptors:: endogenous agonists are in the right place
Good news for CB1 receptors:: endogenous agonists are in the right place
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DOI：
10.1038/sj.bjp.0707566
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发表时间：
2008-01-01
影响因子：
7.3
通讯作者：
Maccarrone, M.
中科院分区：
文献类型：
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作者：
Maccarrone, M.
内源性大麻素是脑型（CB 1）和脾型（CB 2）大麻素受体的内源性配体。N-花生四烯酰乙醇胺（anandamide，AEA）和2-花生四烯酰甘油（2-AG）是两组内源性大麻素脂肪酸酰胺和单酰基甘油的原型成员。与CB 1不同，CB 2受体不存在于“小窝”内，这是一种专门的膜微区，是许多G蛋白偶联受体活性的众所周知的调节剂。在本期《英国药理学杂志》中，Rimmerman及其同事证明2-AG完全位于背根神经节细胞的小窝中，在那里也可以检测到部分AEA（约30%）。然而，大多数AEA（类似于70%）在非小窝组分中检测到，这是CB 2受体定位的地方。AEA和2-AG与膜微区的不同相互作用可能对内源性大麻素依赖的自分泌和/或逆行旁分泌信号通路具有重要意义。它也提出了一个重要的问题，负责不同的定位两个明显相似的内源性大麻素脂质双层内的结构决定因素。
Endocannabinoids are endogenous ligands of brain-type (CB1) and spleen-type (CB2) cannabinoid receptors. N-Arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) are prototype members of the fatty acid amides and the monoacylglycerols, two groups of endocannabinoids. Unlike CB1, CB2 receptors do not reside within 'caveolae', specialized membrane microdomains that are well-known modulators of the activity of a number of G protein-coupled receptors. In this issue of the British Journal of Pharmacology, Rimmerman and coworkers demonstrate that 2-AG is entirely localized in the caveolae of dorsal root ganglion cells, where also part of AEA (similar to 30%) can be detected. However, most of AEA (similar to 70%) was detected in non-caveolae fractions, that is where CB2 receptors are localized. The different interaction of AEA and 2-AG with membrane microdomains might have significant implications for endocannabinoid-dependent autocrine and/or retrograde-paracrine signalling pathways. It also raises an important question about the structural determinants responsible for a different localization of two apparently similar endocannabinoids within lipid bilayers.