Brain regional distribution of endocannabinoids: Implications for their biosynthesis and biological function
Brain regional distribution of endocannabinoids: Implications for their biosynthesis and biological function
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DOI：
10.1006/bbrc.1999.0254
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发表时间：
1999-03-16
影响因子：
3.1
通讯作者：
Di Marzo, V
中科院分区：
文献类型：
--
作者：
Bisogno, T;Berrendero, F;Di Marzo, V
采用同位素稀释气相色谱-质谱法测定了9个大鼠脑区的两种内源性大麻素——花生四烯酰基乙醇酰胺（AEA）和2-花生四烯酰基甘油（2-AG），以及推定的AEA前体n -花生四烯酰基磷脂酰乙醇胺（NArPE）的含量，并与每个区域的大麻素结合位点数量进行了比较。本文首次报道的NArPE与AEA的分布具有良好的相关性，在所有地区，NArPE的代谢物含量都是endocannabinoid的3-13倍。这两种代谢物在脑干和纹状体中含量最高（分别高达358.5和87 pmol/g湿重组织），在间脑、皮层和小脑中含量最低。这些数据支持了一种假设，即在大脑中，AEA是NArPE的代谢产物，可能达到与其所提出的神经调节功能相容的水平。2-AG在脑内的分布也首次被发现与AEA相关，其含量在2.0 ~ 14.0 nmol/g之间（分别在间脑和脑干）。内源性大麻素的分布与大麻素结合位点的分布并不完全匹配，这表明这些化合物不一定在其分子靶点附近产生，或者它们在激活大麻素受体之外发挥功能作用。配体/受体比例的区域差异也可能导致预测相应的受体激活效率差异，如先前的研究所示。(C) 1999学术出版社。
The amounts, in nine different rat brain regions, of the two endocannabinoids, anandamide (arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG), and of the putative AEA precursor N-arachidonoyl-phosphatidylethanolamine (NArPE), were determined by isotope-dilution gas chromatography-mass spectrometry and compared to the number of cannabinoid binding sites in each region. The distribution of NArPE, reported here for the first time, exhibited a good correlation with that of AEA, the former metabolite being 3-13 times more abundant than the endocannabinoid in all regions. The highest amounts of both metabolites (up to 358.5 and 87 pmol/g wet weight tissue, respectively) were found in the brainstem and striatum, and the lowest in the diencephalon, cortex, and cerebellum. These data support the hypothesis that, in the brain, AEA is a metabolic product of NArPE and may reach levels compatible with its proposed neuromodulatory function. The brain distribution of 2-AG, also described in this study for the first time, was found to correlate with that of AEA with levels ranging from 2.0 to 14.0 nmol/g (in the diencephalon and brainstem, respectively). The distribution of the endocannabinoids did not match exactly with that of cannabinoid binding sites, suggesting either that these compounds are not necessarily produced near their molecular targets, or that they play functional roles additional to the activation of cannabinoid receptors. Regional differences in the ligand/receptor ratios may also lead to predict corresponding differences in the efficiency of receptor activation, as shown by previous studies. (C) 1999 Academic Press.