Muscarinic acetylcholine receptor M2 (CHRM2) and Muscarinic acetylcholine receptor M3 (CHRM3) (M2/M3 mAChR)

The Muscarinic acetylcholine receptors M2 and M3 are G-protein-coupled receptors (GPCRs) that play critical roles in the parasympathetic nervous system by responding to the neurotransmitter acetylcholine [1, 2]. The M2 receptor (CHRM2) is primarily coupled to Gi/o proteins and is prominently expressed in the heart, where it mediates bradycardia, and on presynaptic neurons to inhibit acetylcholine release [1, 3]. The M3 receptor (CHRM3) is coupled to Gq/11 proteins and is located in smooth muscles, exocrine glands, and the vascular endothelium, where it mediates contraction and secretion [2, 3]. These receptors are significant therapeutic targets; for instance, M3 antagonism is the primary mechanism for treating chronic obstructive pulmonary disease (COPD) and overactive bladder (OAB) by inducing smooth muscle relaxation [4, 5]. While M3 is often the primary therapeutic goal in these tissues, M2 receptors also contribute to bladder function and airway regulation, making dual M2/M3 or M3-selective ligands common in clinical use [3, 4]. Drugs like tiotropium and oxybutynin interact with these receptors to manage respiratory and urological symptoms, though their use is often limited by systemic anticholinergic side effects such as dry mouth and tachycardia [4, 5].

Other names

CHRM2 and CHRM3Muscarinic M2 and M3 receptorsCholinergic receptor muscarinic 2 and 3M2 and M3 muscarinic acetylcholine receptors

Competitive antagonism of acetylcholine at M2 and M3 muscarinic receptors, leading to smooth muscle relaxation (bronchodilation, bladder relaxation) and decreased glandular secretions [4, 5].