Department of Advanced Life Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan.
Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Int J Mol Sci. 2021 Jan 18;22(2):926. doi: 10.3390/ijms22020926.
Parasympathetic signalling via muscarinic acetylcholine receptors (mAChRs) regulates gastrointestinal smooth muscle function. In most instances, the mAChR population in smooth muscle consists mainly of M and M subtypes in a roughly 80% to 20% mixture. Stimulation of these mAChRs triggers a complex array of biochemical and electrical events in the cell via associated G proteins, leading to smooth muscle contraction and facilitating gastrointestinal motility. Major signalling events induced by mAChRs include adenylyl cyclase inhibition, phosphoinositide hydrolysis, intracellular Ca mobilisation, myofilament Ca sensitisation, generation of non-selective cationic and chloride currents, K current modulation, inhibition or potentiation of voltage-dependent Ca currents and membrane depolarisation. A lack of ligands with a high degree of receptor subtype selectivity and the frequent contribution of multiple receptor subtypes to responses in the same cell type have hampered studies on the signal transduction mechanisms and functions of individual mAChR subtypes. Therefore, novel strategies such as genetic manipulation are required to elucidate both the contributions of specific AChR subtypes to smooth muscle function and the underlying molecular mechanisms. In this article, we review recent studies on muscarinic function in gastrointestinal smooth muscle using mAChR subtype-knockout mice.
副交感神经信号通过毒蕈碱乙酰胆碱受体 (mAChR) 调节胃肠道平滑肌功能。在大多数情况下，平滑肌中的 mAChR 群体主要由 M 和 M 亚型组成，大致比例为 80%至 20%。这些 mAChR 的刺激通过相关的 G 蛋白在细胞中引发一系列复杂的生化和电事件，导致平滑肌收缩并促进胃肠道蠕动。mAChR 诱导的主要信号事件包括腺苷酸环化酶抑制、磷酸肌醇水解、细胞内 Ca 动员、肌丝 Ca 敏化、非选择性阳离子和氯离子电流的产生、K 电流调节、电压依赖性 Ca 电流的抑制或增强以及膜去极化。缺乏具有高受体亚型选择性的配体以及同一细胞类型中多种受体亚型对反应的频繁贡献，阻碍了对单个 mAChR 亚型的信号转导机制和功能的研究。因此，需要采用新的策略，如遗传操作，以阐明特定 AChR 亚型对平滑肌功能的贡献以及潜在的分子机制。在本文中，我们综述了使用 mAChR 亚型敲除小鼠研究胃肠道平滑肌中毒蕈碱功能的最新研究。
