Maccarrone M, Finazzi-Agró A
Department of Biomedical Sciences, University of Teramo, Teramo, Italy.
Cell Death Differ. 2003 Sep;10(9):946-55. doi: 10.1038/sj.cdd.4401284.
Endocannabinoids are a new class of lipid mediators, which include amides, esters and ethers of long-chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the main endogenous agonists of cannabinoid receptors able to mimic several pharmacological effects of Delta-9-tetrahydrocannabinol, the active principle of Cannabis sativa preparations like hashish and marijuana. The pathways leading to the synthesis and release of AEA and 2-AG from neuronal and non-neuronal cells are still rather uncertain. Instead, it is known that the activity of AEA is limited by cellular uptake through a specific membrane transporter, followed by intracellular degradation by a fatty acid amide hydrolase. Together with AEA and congeners these proteins form the 'endocannabinoid system'. Here, the involvement of AEA in apoptosis and the underlying signal transduction pathways will be reviewed, along with the metabolic routes and the molecular targets of this endocannabinoid. Also, recent findings on the apoptotic potential of AEA for neuronal cell differentiation and brain development will be discussed.
内源性大麻素是一类新的脂质介质，包括长链多不饱和脂肪酸的酰胺、酯和醚。花生四烯酸乙醇胺（N-花生四烯酰乙醇胺；AEA）和2-花生四烯酸甘油酯（2-AG）是大麻素受体的主要内源性激动剂，能够模拟大麻（如哈希什和大麻）制剂中的活性成分Δ-9-四氢大麻酚的多种药理作用。神经元和非神经元细胞合成和释放AEA和2-AG的途径仍相当不确定。相反，已知AEA的活性通过特定的膜转运蛋白进行细胞摄取而受到限制，随后被脂肪酸酰胺水解酶进行细胞内降解。这些蛋白质与AEA及其同系物一起构成了“内源性大麻素系统”。在此，将综述AEA在细胞凋亡中的作用及其潜在的信号转导途径，以及这种内源性大麻素的代谢途径和分子靶点。此外，还将讨论AEA对神经元细胞分化和大脑发育的凋亡潜能的最新研究发现。
