Muscarinic acetylcholine receptors M1-M3 (M1-M3 mAChR)

The M1–M3 muscarinic receptors are a subset of the five muscarinic acetylcholine receptor (mAChR) subtypes (M1–M5), which are G protein-coupled receptors (GPCRs) that mediate the effects of the neurotransmitter acetylcholine in the central and peripheral nervous systems [1, 8]. M1 and M3 receptors are primarily coupled to Gq proteins, leading to the activation of phospholipase C and an increase in intracellular calcium, whereas M2 receptors are coupled to Gi proteins, which inhibit adenylyl cyclase and decrease cAMP levels [4, 8]. These receptors play critical roles in diverse physiological processes: M1 is essential for cognitive functions like memory and learning; M2 regulates cardiac rhythm by slowing the heart rate; and M3 mediates smooth muscle contraction in the airways, gastrointestinal tract, and bladder, as well as glandular secretions [1, 4, 6]. Dysregulation of these receptors is implicated in various conditions, including Alzheimer's disease, schizophrenia, chronic obstructive pulmonary disease (COPD), and overactive bladder [2, 3, 10]. Pharmacological modulation of M1–M3 receptors involves a wide range of agonists and antagonists used to treat glaucoma, dry mouth, urinary incontinence, and respiratory disorders, though non-selective agents often carry significant side effects such as dry mouth, tachycardia, and cognitive impairment [1, 6, 15].

Other names

CHRM1CHRM2CHRM3Muscarinic acetylcholine receptor 1Muscarinic acetylcholine receptor 2Muscarinic acetylcholine receptor 3mAChR M1-M3Muscarinic receptors 1-3

M1 and M3 receptors act as Gq-coupled receptors that activate phospholipase C, leading to increased intracellular calcium and smooth muscle contraction or glandular secretion, while M2 receptors act as Gi-coupled receptors that inhibit adenylyl cyclase, reducing cAMP levels and slowing heart rate [1, 4, 8].