Kazan Institute of Biochemistry and Biophysics FRC Kazan Scientific Center of RAS, PB 30, Kazan 420111, Russia.
Kazan Institute of Biochemistry and Biophysics FRC Kazan Scientific Center of RAS, PB 30, Kazan 420111, Russia.
Mol Cell Neurosci. 2020 Oct;108:103550. doi: 10.1016/j.mcn.2020.103550. Epub 2020 Sep 2.
The studies of the interaction between the sympathetic and motor nervous systems are extremely relevant due to therapy for many neurodegenerative and cardiovascular disorders involving adrenergic compounds. Evidences indicate close contact between sympathetic varicosities and neuromuscular synapses. This raises questions about the effects of catecholamines on synaptic transmission. The currently available information is contradictory, and the types of adrenoreceptors responsible for modulation of neurotransmitter release have not been identified in mammalian neuromuscular synapses. Our results have shown that the α1A, α1B, α2A, α2B, α2C, and β1 adrenoreceptor subtypes are expressed in mouse diaphragm muscle containing neuromuscular synapses and sympathetic varicosities. Pharmacological stimulation of adrenoreceptors affects both spontaneous and evoked acetylcholine quantal secretion. Agonists of the α1, α2 and β1 adrenoreceptors decrease spontaneous release. Activation of the α2 and β1 adrenoreceptors reduces the number of acetylcholine quanta released in response to a nerve stimulus (quantal content), but an agonist of the β2 receptors increases quantal content. Activation of α2 and β2 adrenoreceptors alters the kinetics of acetylcholine quantal release by desynchronizing the neurosecretory process. Specific blockers of these receptors eliminate the effects of the specific agonists. The action of blockers on quantal acetylcholine secretion indicates possible action of endogenous catecholamines on neuromuscular transmission. Elucidating the molecular mechanisms by which clinically utilized adrenomimetics and adrenoblockers regulate synaptic vesicle release at the motor axon terminal will lead to the creation of improved and safer sympathomimetics for the treatment of various neurodegenerative diseases with synaptic defects.
由于涉及儿茶酚胺化合物的许多神经退行性和心血管疾病的治疗，交感和运动神经系统之间相互作用的研究极其重要。有证据表明交感神经末梢和运动神经元突触之间有密切的接触。这就提出了儿茶酚胺对突触传递的影响的问题。目前可获得的信息是相互矛盾的，并且在哺乳动物运动神经元突触中负责调节神经递质释放的肾上腺素能受体的类型尚未确定。我们的研究结果表明，α1A、α1B、α2A、α2B、α2C 和 β1 肾上腺素受体亚型在含有运动神经元突触和交感神经末梢的小鼠膈肌肌肉中表达。肾上腺素能受体的药理学刺激影响自发性和诱发的乙酰胆碱量子分泌。α1、α2 和 β1 肾上腺素受体激动剂减少自发性释放。α2 和 β1 肾上腺素受体的激活减少了对神经刺激（量子含量）释放的乙酰胆碱量子数量，但β2 受体的激动剂增加了量子含量。α2 和 β2 肾上腺素受体的激活通过使神经分泌过程不同步来改变乙酰胆碱量子释放的动力学。这些受体的特异性阻断剂消除了特定激动剂的作用。这些阻断剂对量子乙酰胆碱分泌的作用表明内源性儿茶酚胺对神经肌肉传递可能有作用。阐明临床上使用的拟交感神经药和肾上腺素能阻断剂调节运动轴突末端突触小泡释放的分子机制，将导致为治疗具有突触缺陷的各种神经退行性疾病而创造出更好和更安全的拟交感神经药。
