Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Mol Neurobiol. 2012 Oct;46(2):374-92. doi: 10.1007/s12035-012-8299-0. Epub 2012 Jul 17.
Since the discovery of endocannabinoids and their receptors, two major members of the endocannabinoid family, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), have been regarded almost as twin brothers. Pharmacological properties were initially considered to be similar, as these molecules were believed mutually exchangeable and almost indistinguishable in the regulation of synaptic functions, such as long- and short-term synaptic plasticity, and in behavioral aspects, such as learning and memory, reward and addiction, antinociception, and anxiety. In recent years, however, endocannabinoid signaling specificity began to emerge, in particular, due to the production of genetically engineered mice lacking key enzymes in endocannabinoid synthesis or degradation, together with the development of selective inhibitors of AEA or 2-AG catabolic enzymes. Evidence now suggests that AEA and 2-AG possess specific pharmacological properties, are engaged in different forms of synaptic plasticity, and take part in different behavioral functions. In this review, we provide an overview on similarities and specificities of the two endocannabinoids in the CNS and on the unresolved questions concerning their role in synaptic signaling.
自从内源性大麻素及其受体被发现以来，内源性大麻素家族的两个主要成员——花生四烯酸乙醇胺（AEA）和 2-花生四烯酰甘油（2-AG）——几乎被视为双胞胎兄弟。最初认为这些分子的药理学特性相似，因为人们认为它们在调节突触功能（如长时程和短时程突触可塑性）以及行为方面（如学习和记忆、奖励和成瘾、镇痛和焦虑）是可以相互交换且几乎无法区分的。然而，近年来，内源性大麻素信号传递的特异性开始显现，特别是由于缺乏内源性大麻素合成或降解关键酶的基因工程小鼠的产生，以及 AEA 或 2-AG 代谢酶的选择性抑制剂的开发。现在有证据表明，AEA 和 2-AG 具有特定的药理学特性，参与不同形式的突触可塑性，并参与不同的行为功能。在这篇综述中，我们概述了这两种内源性大麻素在中枢神经系统中的相似性和特异性，以及它们在突触信号传递中的作用所存在的未解决问题。
