Metabolism of anandamide and 2-arachidonoylglycerol: An historical overview and some recent developments
Metabolism of anandamide and 2-arachidonoylglycerol: An historical overview and some recent developments
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DOI：
10.1007/bf02562332
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发表时间：
1999-01-01
期刊：
影响因子：
1.9
通讯作者：
Melck, D
中科院分区：
文献类型：
--
作者：
Di Marzo, V;De Petrocellis, L;Melck, D
花生四烯酸乙醇胺（N-arachidonoyethanolamine）和2-arachidonoyl glycerol是迄今发现的大麻素受体的两种内源性激动剂。与其他类二十烷酸一样，并且与经典的神经调节剂不同，这两种化合物由神经元按需合成，即，它们的生物合成而不是释放受到Ca 2+内流和细胞膜去极化的刺激。这两种内源性大麻素都可以通过磷脂酶的作用从膜磷酸甘油酯产生，尽管也提出了从头途径。一旦被细胞释放，花生四烯酸和2-花生四烯酸甘油的作用在它们扩散通过细胞膜之后通过酰胺或酯键的水解而终止，产生花生四烯酸，然后花生四烯酸立即重新结合到磷脂中。一种酶，脂肪酸酰胺水解酶，催化神经和非神经细胞中内源性大麻素的水解。这种酶也识别N-棕榈酰乙醇胺，一种花生四烯酸的同系物，其催化效率取决于所研究的细胞类型。然而，对花生四烯酸和N-棕榈酰乙醇胺具有不同亲和力的不同同工酶的存在还没有研究。此外，很少有工作已经进行的花生四烯酸形成和分解的调节，和几个悬而未决的问题仍然是大麻拟2-花生四烯酸甘油在有核血细胞，如巨噬细胞的可能的生物合成和降解机制。最后，两种内源性大麻素在无脊椎动物中的共存尚未完全确定。在这里，我们简要地回顾了艺术的石板，并提出了新的数据，从我们的实验室，这四个基本上未开发的方面endacannabinoid代谢。
Anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol are the two endogenous agonists of cannabinoid receptors discovered to date. Like other eicosanoids, and unlike classical neuromodulators, these two compounds are synthesized by neurons on demand, i.e., their biosynthesis, rather than release, is stimulated by Ca2+ influx and cell membrane depolarization. Both endocannabinoids can be produced from membrane phosphoglycerides through the action of phospholipases, although de novo pathways have also been suggested. Once released by cells, the action of both anandamide and 2-arachidonoylglycerol is terminated-after their diffusion through the cell membrane-by the hydrolysis of the amide or ester bonds to yield arachidonic acid, which is then immediately reincorporated into phospholipids. One enzyme, fatty acid amide hydrolase, catalyzes the hydrolysis of both endocannabinoids in nervous and nonnervous cells. This enzyme also recognizes N-palmitoylethanolamine, an antiinflammatory congener of anandamide, with a catalytic efficiency that depends on the cell type under study. However, the existence of different isozymes with different affinity far anandamide and N-palmitoylethanolamine has not been investigated. Moreover, little work has been performed on the regulation of anandamide formation and breakdown, and several open questions remain as to the possible biosynthetic and degradative mechanisms of cannabimimetic 2-arachidonoylglycerol in nucleated blood cells such as macrophages. Finally, the co-existence of both endocannabinoids in invertebrates has not been fully established. Here we briefly review the slate of the art, and present new data from our laboratory, on these four largely unexplored aspects of endacannabinoid metabolism.