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Интеллектуальная Система Тематического Исследования НАукометрических данных |
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2-arachidonoyl-glycerol (2-AG) is a widely studied endocannabinoid. In the central nervous system this substance acts as retrograde regulator which generally suppresses transmitter release by acting on CB-receptors of the presynaptic terminal. In peripheral neuromuscular junctions (NMJs) we were the first to show that exogenous application of 2-AG leads to an increase in the amplitude of miniature end plate potentials (MEPPs) through CB1-receptor activation and thereby potentiates synaptic transmission. The following work was focused on elucidating the mechanisms of such a 2-AG-mediated potentiation of the activity of NMJs. Experiments were conducted on isolated neuromuscular preparations of mice semidiaphragms with use of the standard microelectrode technique of intracellular biopotential registration. Obtained data was further analyzed in MiniAnalysis (Synaptosoft, United States) and GraphPad Prism 6.0.The increase in MEPP amplitude caused by 2-AG (1 μM) was completely prevented by vesamicol (1 μM) which is a blocker of the vesicular acetylcholine transporter. Thus, 2-AG potentiates synaptic transmission by increasing the size of the quantum of acetylcholine (ACh).PKA inhibition by H-89 (1 μM) also prevented the 2-AG mediated increase in MEPP amplitude,indicating that PKA is a part of a signaling pathway which is triggered by 2-AG action and leads to an upregulation of ACh pumping into vesicles. We previously observed such PKA-dependent increase in the size of ACh quanta upon CGRP-receptor activation. This made us wonder whether CGRP-receptors are also involved in the effects of 2-AG. Blocking CGRP-receptors with CGRP8-37 completely averted the effects of 2-AG on MEPP amplitude. Thus, we are the first to show an involvement of CGRP-receptors in the 2-AG-induced potentiation of ACh release in mouse NMJs. The details of the intertwining of CGRP-mediated and 2-AG-mediated signaling pathways in mouse motor synapses is the subject of further research.