Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala
Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala
复制标题
DOI：
10.1111/j.1460-9568.2004.03428.x
复制
发表时间：
2004-07-01
影响因子：
3.4
通讯作者：
Freund, TF
中科院分区：
文献类型：
--
作者：
Gulyas, AI;Cravatt, BF;Freund, TF
脂肪酸酰胺水解酶(FAAH)和单甘酯脂肪酶(MGL)催化内源性大麻酰胺和2-花生四烯酸甘油的水解酶。我们研究了它们在已知大麻素受体激活的定位和影响的脑区的超微结构分布。在海马区，FAAH存在于主细胞的胞体和树突中，而不存在于中间神经元中。它主要位于细胞内储存钙离子的细胞器(如线粒体、光滑内质网)的膜表面，较少分布在体细胞或树突质膜上。MGL免疫反应见于颗粒细胞、CA3锥体细胞和部分中间神经元的轴突终末。在小脑中，浦肯野细胞及其树突呈FAAH阳性反应，在浦肯野细胞/颗粒细胞层的交界处有稀疏的轴突丛。MGL的免疫染色是互补的，分子层的轴突被密集标记，留下了浦肯野细胞树突的空白。FAAH在杏仁核的分布类似于CB1大麻素受体：在基底外侧核的神经元胞体和近侧树突中有明显的信号，在中央核几乎没有标记。MGL染色仅局限于神经束中的轴突，FAAH在不同的核团中的相对信号强度相似。因此，FAAH主要是突触后酶，而MGL是突触前酶。FAAH与细胞质细胞器的膜有关。这两种酶的不同区划表明，anandamide和2-AG信号可能从属于至少在新陈代谢阶段空间分离的功能角色。
Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) catalyse the hydrolysis of the endocannabinoids anandamide and 2-arachidonoyl glycerol. We investigated their ultrastructural distribution in brain areas where the localization and effects of cannabinoid receptor activation are known. In the hippocampus, FAAH was present in somata and dendrites of principal cells, but not in interneurons. It was located mostly on the membrane surface of intracellular organelles known to store Ca2+ (e.g. mitochondria, smooth endoplasmic reticulum), less frequently on the somatic or dendritic plasma membrane. MGL immunoreactivity was found in axon terminals of granule cells, CA3 pyramidal cells and some interneurons. In the cerebellum, Purkinje cells and their dendrites are intensively immunoreactive for FAAH, together with a sparse axon plexus at the border of the Purkinje cell/granule cell layers. Immunostaining for MGL was complementary, the axons in the molecular layer were intensively labelled leaving the Purkinje cell dendrites blank. FAAH distribution in the amygdala was similar to that of the CB1 cannabinoid receptor: evident signal in neuronal somata and proximal dendrites in the basolateral nucleus, and hardly any labelling in the central nucleus. MGL staining was restricted to axons in the neuropil, with similar relative signal intensities seen for FAAH in different nuclei. Thus, FAAH is primarily a postsynaptic enzyme, whereas MGL is presynaptic. FAAH is associated with membranes of cytoplasmic organelles. The differential compartmentalization of the two enzymes suggests that anandamide and 2-AG signalling may subserve functional roles that are spatially segregated at least at the stage of metabolism.