Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore Street, Rm 5-025, Baltimore, MD 21201, USA.
J Physiol. 2012 May 15;590(10):2203-12. doi: 10.1113/jphysiol.2011.220855. Epub 2012 Jan 30.
Endogenous cannabinoids (endocannabinoids, eCBs) are ubiquitous regulators of synaptic transmission in the brain, mediating numerous forms of short- and long-term plasticity, and having strong influences on synapse formation and neurogenesis. Their roles as retrograde messengers that suppress both excitatory and inhibitory transmission are well-established. Yet, despite intensive investigation, many basic aspects of the eCB system are not understood. This brief review highlights recent advances, problems that remain unresolved, and avenues for future exploration. While 2-arachidonoylglycerol (2-AG) is probably the major eCB for intercellular CB1R-dependent signalling, anandamide (AEA) has come to the forefront in several novel contexts, both as a dual endovanilloid/endocannabinoid that regulates synaptic transmission acutely and as the source of a steady eCB tone in hippocampus. Complexities in the cellular processing of 2-AG are receiving renewed attention, as they are increasingly recognized as major determinants of how 2-AG affects cells. Long-standing fundamental issues such as the synthesis pathway for AEA and the molecular mechanism(s) underlying cellular uptake and release of eCBs remain problematical.
内源性大麻素（内源性大麻素，eCBs）是大脑中突触传递的普遍调节剂，介导多种形式的短期和长期可塑性，对突触形成和神经发生有强烈影响。它们作为逆行信使的作用，抑制兴奋和抑制性传递，这已经得到了很好的确立。然而，尽管进行了深入的研究，eCB 系统的许多基本方面仍未得到理解。这篇简短的综述强调了最近的进展、仍然存在的未解决的问题以及未来探索的途径。虽然 2-花生四烯酸甘油（2-AG）可能是细胞间 CB1R 依赖性信号传导的主要 eCB，但在几个新的背景下，大麻素（AEA）已成为焦点，既是一种双重香草素/内源性大麻素，可急性调节突触传递，又是海马中稳定的 eCB 音调的来源。2-AG 的细胞处理的复杂性正在受到新的关注，因为它们越来越被认为是 2-AG 如何影响细胞的主要决定因素。一些长期存在的基本问题，如 AEA 的合成途径以及细胞摄取和释放 eCB 的分子机制，仍然存在问题。
