Arkhipov Arsenii, Zhilyakov Nikita, Sibgatullina Guzel, Nevsky Egor, Bukharaeva Ellya A, Petrov Alexey M
Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan, Scientific Center of RAS, 2/31 Lobachevsky St, Kazan, RT, Russia, 420111.
Kazan State Medical University, 49 Butlerova St, Kazan, RT, Russia, 420012.
Neurochem Res. 2025 May 12;50(3):162. doi: 10.1007/s11064-025-04415-w.
The sympathoadrenal system functions as an adaptive and trophic system, ensuring increased vitality in humans and animals. Recent findings suggest that, in addition to its effects on muscle tissue, neuromuscular junctions (NMJs) may represent an important target for action of sympathetic mediators. Here, we presented experimental data on neurotransmitter release modulation by adrenergic ligands at the NMJs of mouse fast-twitch skeletal muscle levator auris longus. Adrenaline (but not noradrenaline) increased both spontaneous and evoked acetylcholine (ACh) release. This effect of adrenaline was accompanied by an increase in action potential-elicited Ca entry into motor nerve terminals. Blockage of adenylate cyclase and protein kinase A (but not Na, K-ATPase) prevented the facilitatory effect of adrenaline on ACh release. Sympathetic nerves as well as immunoexpression of α1-, α2- and β1-, β2-adrenoceptors (ARs) were revealed in close proximity to the NMJs. Agonists of α2- and β1-ARs had no marked presynaptic effects. α1-AR activation reduced spontaneous and evoked ACh release in a phospholipase A and protein kinase C-dependent manner. Effects of β2-AR activation were dependent on the type of agonist: Procaterol decreased both ACh release and Ca entry into the nerve terminals, whereas fenoterol promoted ACh release in a G protein-dependent manner. Thus, synaptic transmission in the "fast" NMJs had specific features of adrenergic regulation engaging G protein, adenylyl cyclase, phospholipase A, protein kinases A and C. The positive effect of natural agonist adrenaline was reproduced only by β2-AR activation with fenoterol, but not α1-, α2-, β1-agonists and β2-agonist procaterol.
交感肾上腺系统作为一个适应性和营养性系统发挥作用，确保人和动物活力增强。最近的研究结果表明，除了对肌肉组织的作用外，神经肌肉接头（NMJ）可能是交感神经介质作用的重要靶点。在此，我们展示了肾上腺素能配体对小鼠快肌骨骼肌耳长提肌神经肌肉接头处神经递质释放调节的实验数据。肾上腺素（而非去甲肾上腺素）增加了自发和诱发的乙酰胆碱（ACh）释放。肾上腺素的这种作用伴随着动作电位引发的Ca进入运动神经末梢的增加。腺苷酸环化酶和蛋白激酶A（而非钠钾ATP酶）的阻断阻止了肾上腺素对ACh释放的促进作用。在神经肌肉接头附近发现了交感神经以及α1-、α2-和β1-、β2-肾上腺素能受体（ARs）的免疫表达。α2-和β1-ARs激动剂没有明显的突触前效应。α1-AR激活以磷脂酶A和蛋白激酶C依赖的方式减少自发和诱发的ACh释放。β2-AR激活的效应取决于激动剂的类型：丙卡特罗减少ACh释放和Ca进入神经末梢，而非诺特罗以G蛋白依赖的方式促进ACh释放。因此，“快速”神经肌肉接头处的突触传递具有涉及G蛋白、腺苷酸环化酶、磷脂酶A、蛋白激酶A和C的肾上腺素能调节的特定特征。天然激动剂肾上腺素的积极作用仅通过非诺特罗激活β2-AR得以重现，而α1-、α2-、β1-激动剂和β2-激动剂丙卡特罗则不能。
