Muscarinic acetylcholine receptors (M1-M4) (M1-M4)

Muscarinic acetylcholine receptors M1, M2, M3, and M4 are members of the G protein-coupled receptor (GPCR) family, specifically the class A (rhodopsin-like) receptors, widely expressed in the central and peripheral nervous systems as well as multiple organs[1][2][3][4][5]. They mediate the cellular effects of the neurotransmitter acetylcholine via coupling to different classes of G proteins: odd-numbered subtypes (M1, M3) mainly couple to Gq/11, leading to excitation via phospholipase C activation and increased intracellular calcium, while even-numbered subtypes (M2, M4) couple to Gi/o, leading to inhibitory cellular effects by decreasing adenylyl cyclase activity and cAMP levels[1][3][5]. Each subtype exerts specific physiological functions, such as regulation of cognitive processes (M1), cardiac function (M2), smooth muscle contraction and glandular secretion (M3), and dopaminergic as well as hematopoietic regulation (M4)[1][2][4]. Muscarinic receptors are key therapeutic targets in diseases including neurodegenerative, cardiovascular, respiratory, and urinary disorders, with both agonists and antagonists used in clinical practice[2][3][4].

Other names

mAChR M1mAChR M2mAChR M3mAChR M4Cholinergic receptor muscarinic 1Cholinergic receptor muscarinic 2Cholinergic receptor muscarinic 3Cholinergic receptor muscarinic 4Muscarinic receptor 1Muscarinic receptor 2Muscarinic receptor 3Muscarinic receptor 4

Antagonists inhibit acetylcholine-mediated signal transduction, reducing glandular secretion, smooth muscle contraction, or modulating cardiac/neuronal activity Agonists activate muscarinic receptors to mimic acetylcholine effects in peripheral and central tissues Selective subtype modulation (e.g., M3 antagonism for overactive bladder; M1 activation for cognitive enhancement)