Hillard C J, Campbell W B
Department of Pharmacology, Medical College of Wisconsin, Milwaukee 53226, USA.
J Lipid Res. 1997 Dec;38(12):2383-98.
This review presents and explores the hypothesis that N-arachidonylethanolamine (AEA, also called anandamide) is synthesized in the brain and functions as an endogenous ligand of the cannabinoid receptor. Support for this hypothesis comes from in vitro experiments demonstrating that AEA binds and activates signaling through the cannabinoid receptor. In addition, in vivo AEA produces effects very similar to those of the classical agonists of the cannabinoid receptor. Evidence for the cellular synthesis and release of AEA is not as clear. Data are presented that suggest that AEA is synthesized via a two enzyme process. First, a novel phospholipid (N-arachidonylphosphatidylethanolamine) is formed by a calcium-dependent transacylase. This lipid is a substrate for a phosphodiesterase of the phospholipase D type which releases AEA. Although there is some evidence to support this hypothesis, it is clear that AEA is a very minor product of this enzymatic cascade. Several important questions remain to be answered, including whether the concentrations of AEA synthesized by cells are sufficient to support a signaling role in the brain.
N-花生四烯酸乙醇胺（AEA，也称为花生四烯酸酰胺）在大脑中合成，并作为大麻素受体的内源性配体发挥作用。对这一假说的支持来自体外实验，这些实验表明AEA能结合并激活通过大麻素受体的信号传导。此外，体内的AEA产生的效应与大麻素受体经典激动剂的效应非常相似。关于AEA在细胞内合成和释放的证据并不那么明确。所呈现的数据表明AEA是通过一个双酶过程合成的。首先，一种新型磷脂（N-花生四烯酰磷脂酰乙醇胺）由一种钙依赖性转酰基酶形成。这种脂质是磷脂酶D型磷酸二酯酶的底物，该酶可释放AEA。尽管有一些证据支持这一假说，但很明显AEA是这种酶促级联反应的极少量产物。几个重要问题仍有待解答，包括细胞合成的AEA浓度是否足以支持其在大脑中的信号传导作用。
