Muscarinic acetylcholine receptors M2–M5 (mAChR M2–M5)

The muscarinic acetylcholine receptors M2–M5 are a group of four G protein-coupled receptors (GPCRs) that mediate the physiological responses to acetylcholine in various tissues [3, 7]. These receptors are divided into two signaling classes: the Gi-coupled M2 and M4 receptors, which inhibit adenylyl cyclase to decrease cAMP, and the Gq-coupled M3 and M5 receptors, which activate phospholipase C to increase intracellular calcium [1, 6]. M2 receptors are primarily found in the heart, where they slow the heart rate, while M3 receptors are essential for smooth muscle contraction in the lungs and bladder and for stimulating secretions from exocrine glands [1, 2]. M4 and M5 receptors are predominantly expressed in the central nervous system, playing critical roles in modulating dopaminergic pathways and cognitive functions [4, 5]. Clinically, these receptors are targets for a wide range of conditions; for instance, M3 antagonists are used to treat COPD and overactive bladder, while M4 agonists are being developed as novel antipsychotics for schizophrenia [3, 6, 10]. A major challenge in drug development is achieving subtype selectivity to avoid side effects such as dry mouth (M3) or cardiovascular disturbances (M2) [4, 8]. Recent advancements include the development of allosteric modulators that offer higher selectivity than traditional orthosteric ligands [5, 7].

Other names

Cholinergic receptor muscarinic 2Cholinergic receptor muscarinic 3Cholinergic receptor muscarinic 4Cholinergic receptor muscarinic 5CHRM2CHRM3CHRM4CHRM5mAChR M2mAChR M3mAChR M4mAChR M5Muscarinic receptors 2-5

M2 and M4 receptors couple to Gi/o proteins to inhibit adenylyl cyclase and decrease cAMP, while M3 and M5 receptors couple to Gq/11 proteins to activate phospholipase C and increase intracellular calcium.