Abstract

This review focuses on new aspects of endocannabinoid functions and mechanisms of activity in central and peripheral synapses, different from the general viewpoint that endocannabinoids are retrograde signaling molecules, which inhibit neurotransmitter release by activating specific presynaptic endocannabinoid receptors CB1 and CB2. Biased agonism of the endogenous and synthetic cannabinoids as well as ability of the CB-receptors to couple not only with classical G_i-proteins, but also with G_s- and G_q-proteins and, moreover, with β-arrestins (thereby triggering additional signaling pathways in synapses) are described here in detail. Examples of noncanonical tonic activity of endocannabinoids and their receptors and their role in synaptic function are also presented. The role of endocannabinoids in short-term and long-term potentiation of neurotransmitter release in central synapses and their facilitating effect on quantal size and other parameters of acetylcholine release in mammalian neuromuscular junctions are highlighted in this review. In conclusion, it is stated that the endocannabinoid system has a wider range of various multidirectional modulating effects (both potentiating and inhibiting) on neurotransmitter release than initially recognized. Re-evaluation of the functions of endocannabinoid system with consideration of its noncanonical features will lead to better understanding of its role in the normal and pathological functioning of the nervous system and other systems of the body, which has an enormous practical value.

中文翻译：

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内源性大麻素及其受体在中枢和外周突触中的非经典活性

摘要

本综述重点关注中枢和外周突触中内源性大麻素功能和活动机制的新方面，不同于内源性大麻素是逆行信号分子的一般观点，后者通过激活特定的突触前内源性大麻素受体 CB1 和 CB2 来抑制神经递质释放。内源性和合成大麻素的偏向激动作用以及 CB 受体不仅与经典 G _i蛋白偶联的能力，还与 G _s - 和 G _q偶联β-抑制蛋白（从而在突触中触发额外的信号通路）在此处详细描述。还介绍了内源性大麻素及其受体的非经典滋补活性及其在突触功能中的作用的例子。本综述强调了内源性大麻素在中枢突触中神经递质释放的短期和长期增强中的作用及其对哺乳动物神经肌肉接头中乙酰胆碱释放的量子大小和其他参数的促进作用。总之，据说内源性大麻素系统对神经递质释放的各种多向调节作用（增强和抑制）比最初认识到的范围更广。