Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice

• Published in: International journal of molecular sciences 2021-01, Vol.22 (2), p.926
• Main Authors: Tanahashi, Yasuyuki, Komori, Seiichi, Matsuyama, Hayato, Kitazawa, Takio, Unno, Toshihiro
• Format: Article
• Language: English
• Subjects: Adenylate cyclase; Animals; Bladder; Calcium (intracellular); Calcium channels (voltage-gated); Calcium currents; Calcium ions; Chloride currents; Current modulation; Depolarization; Gastric motility; gastrointestinal tract; Gastrointestinal Tract - growth & development; Gastrointestinal Tract - metabolism; Gastrointestinal Tract - pathology; GTP-Binding Proteins - genetics; Intracellular signalling; Kinases; knockout mouse; Mice; Mice, Knockout - genetics; Molecular modelling; muscarinic receptor subtypes; Muscle contraction; Muscle Contraction - genetics; Muscle, Smooth - growth & development; Muscle, Smooth - metabolism; Muscles; Muscular function; non-selective cationic channels; Parasympathetic nervous system; Physiology; Proteins; Receptor mechanisms; Receptor, Muscarinic M2 - genetics; Receptor, Muscarinic M3 - genetics; Review; Rodents; Selectivity; Signal transduction; Signal Transduction - genetics; signal transduction pathways; Smooth muscle
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.