Muscarinic acetylcholine receptor M2, M3, and M4 (mAChR M2-M4) (mAChR M2-M4)

The muscarinic acetylcholine receptors M2, M3, and M4 are a subset of the five muscarinic receptor subtypes (M1–M5) that belong to the G protein-coupled receptor (GPCR) superfamily [1.2.1, 1.3.5]. These receptors are activated by the endogenous neurotransmitter acetylcholine and play diverse roles in both the central and peripheral nervous systems [1.2.3]. The M2 and M4 subtypes are primarily coupled to the Gi/o family of G proteins, which inhibit adenylyl cyclase and decrease intracellular cAMP levels, whereas the M3 subtype is coupled to Gq/11 proteins, leading to the activation of phospholipase C and an increase in intracellular calcium [1.2.3, 1.3.5]. M2 receptors are critical for regulating cardiac function, specifically slowing heart rate, and also act as presynaptic autoreceptors in the brain [1.1.2, 1.4.1]. M3 receptors are widely expressed in smooth muscles and exocrine glands, where they mediate contraction (e.g., in the airways and bladder) and secretion (e.g., saliva and gastric acid) [1.3.1, 1.4.3]. M4 receptors are predominantly located in the central nervous system, particularly in the striatum, where they modulate dopaminergic activity and are involved in motor control and cognitive processes [1.3.3, 1.4.1]. These receptors are major therapeutic targets for a variety of conditions, including respiratory diseases like COPD (M3 antagonists), overactive bladder (M3 antagonists), and neuropsychiatric disorders like schizophrenia (M4 agonists) [1.3.1, 1.3.3].

Other names

CHRM2CHRM3CHRM4Cholinergic receptor muscarinic 2Cholinergic receptor muscarinic 3Cholinergic receptor muscarinic 4M2 muscarinic receptorM3 muscarinic receptorM4 muscarinic receptormAChR M2mAChR M3mAChR M4

Agonism, Antagonism, and Allosteric modulation of G protein-coupled signaling pathways. M2 and M4 receptors signal through Gi/o proteins to inhibit adenylyl cyclase and reduce cAMP, while M3 receptors signal through Gq/11 proteins to activate phospholipase C and increase intracellular calcium [1.2.3, 1.3.5].