Department of Molecular Neuroimmune Signaling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Int J Mol Sci. 2023 Mar 30;24(7):6524. doi: 10.3390/ijms24076524.
Nicotinic acetylcholine receptors (nAChRs) present as many different subtypes in the nervous and immune systems, muscles and on the cells of other organs. In the immune system, inflammation is regulated via the vagus nerve through the activation of the non-neuronal α7 nAChR subtype, affecting the production of cytokines. The analgesic properties of α7 nAChR-selective compounds are mostly based on the activation of the cholinergic anti-inflammatory pathway. The molecular mechanism of neuropathic pain relief mediated by the inhibition of α9-containing nAChRs is not fully understood yet, but the role of immune factors in this process is becoming evident. To obtain appropriate drugs, a search of selective agonists, antagonists and modulators of α7- and α9-containing nAChRs is underway. The naturally occurring three-finger snake α-neurotoxins and mammalian Ly6/uPAR proteins, as well as neurotoxic peptides α-conotoxins, are not only sophisticated tools in research on nAChRs but are also considered as potential medicines. In particular, the inhibition of the α9-containing nAChRs by α-conotoxins may be a pathway to alleviate neuropathic pain. nAChRs are involved in the inflammation processes during AIDS and other viral infections; thus they can also be means used in drug design. In this review, we discuss the role of α7- and α9-containing nAChRs in the immune processes and in pain.
烟碱型乙酰胆碱受体 (nAChRs) 在神经系统和免疫系统、肌肉以及其他器官的细胞中呈现出许多不同的亚型。在免疫系统中，炎症通过迷走神经的激活得到调节，这种激活作用是通过非神经元α7 nAChR 亚型实现的，它影响细胞因子的产生。α7 nAChR 选择性化合物的镇痛特性主要基于胆碱能抗炎途径的激活。抑制包含α9 的 nAChRs 介导的神经性疼痛缓解的分子机制尚未完全了解，但免疫因素在这一过程中的作用正变得明显。为了获得合适的药物，正在寻找选择性激动剂、拮抗剂和包含α7 和α9 的 nAChRs 的调节剂。天然存在的三指蛇α-神经毒素和哺乳动物 Ly6/uPAR 蛋白，以及神经毒性肽α-芋螺毒素，不仅是 nAChRs 研究的精巧工具，也被认为是潜在的药物。特别是，α-芋螺毒素对包含α9 的 nAChRs 的抑制可能是缓解神经性疼痛的一种途径。nAChRs 参与艾滋病和其他病毒感染期间的炎症过程；因此，它们也可以成为药物设计的手段。在这篇综述中，我们讨论了包含α7 和α9 的 nAChRs 在免疫过程和疼痛中的作用。
