Romero J, Hillard C J, Calero M, Rábano A
Laboratorio de Apoyo a la Investigación, Fundación Hospital Alcorcón, Alcorcón, 28922 Madrid, Spain.
Brain Res Mol Brain Res. 2002 Apr 30;100(1-2):85-93. doi: 10.1016/s0169-328x(02)00167-5.
Recent discoveries have opened new fields for research on the biochemistry and pharmacology of cannabinoids. Among them, and most importantly, are the characterization and molecular cloning of central and peripheral cannabinoid receptors as well as the isolation of the first putative endogenous ligands that bind to them, anandamide and 2-arachidonylglycerol. The enzyme that degrades these so-called "endocannabinoids" is an integral membrane protein, fatty acid amide hydrolase. Its distribution and biochemistry in rat brain suggest that it plays a critical role in the regulation of the endocannabinoid system. However, few data exist regarding its distribution and mechanism of action in human tissues. To that end, we have studied its cellular distribution in the human central nervous system by immunohistochemistry. Using an affinity-purified antibody, we report that fatty acid amide hydrolase is localized to specific and well-delimited cell populations, including cortical pyramidal neurons, subcortical white matter astrocytes, striatal and striatoefferent projecting neurons, hypothalamic and midbrain nuclei, granular and molecular layers of the cerebellum, Purkinje neurons, dentate cerebellar nucleus, inferior olivary nuclei and others. This distribution resembles that of the central cannabinoid receptors as well as that of the enzyme distribution in the rat brain. In summary, the cellular localization of the degradative enzyme of the endogenous cannabinoid ligands in human central nervous system reveals its presence on both neuronal and glial elements and shows a significant overlapping with that of central cannabinoid receptors, mainly in areas related with motor control, confirming the notion that the endocannabinoid system plays a critical role in the control of movement.
最近的发现为大麻素的生物化学和药理学研究开辟了新领域。其中，最重要的是中枢和外周大麻素受体的表征和分子克隆，以及与它们结合的首批假定内源性配体——花生四烯乙醇胺和2-花生四烯酸甘油酯的分离。降解这些所谓“内源性大麻素”的酶是一种整合膜蛋白——脂肪酸酰胺水解酶。其在大鼠脑中的分布和生物化学表明，它在调节内源性大麻素系统中起关键作用。然而，关于其在人体组织中的分布和作用机制的数据很少。为此，我们通过免疫组织化学研究了其在人类中枢神经系统中的细胞分布。使用亲和纯化抗体，我们报告脂肪酸酰胺水解酶定位于特定且界限分明的细胞群体，包括皮质锥体细胞、皮质下白质星形胶质细胞、纹状体和纹状体传出投射神经元、下丘脑和中脑核、小脑颗粒层和分子层、浦肯野神经元、齿状小脑核、下橄榄核等。这种分布类似于中枢大麻素受体的分布以及大鼠脑中该酶的分布。总之，内源性大麻素配体降解酶在人类中枢神经系统中的细胞定位揭示了其在神经元和神经胶质成分上的存在，并与中枢大麻素受体的分布有显著重叠，主要在与运动控制相关的区域，证实了内源性大麻素系统在运动控制中起关键作用这一观点。
