Muscarinic acetylcholine receptor 3 (M3R)

Muscarinic acetylcholine receptor 3 (M3, CHRM3) is a G protein-coupled receptor (GPCR) that binds acetylcholine, mediating its biological effects across many tissues. It is highly expressed on smooth muscle, glands (endocrine, exocrine), lung, pancreas, bladder, and key regions in the brain responsible for insulin regulation and emesis[1][7]. Activation of M3 stimulates smooth muscle contraction and glandular secretion, and in pancreatic beta cells is a critical regulator of insulin secretion and glucose homeostasis[1][2]. It couples to the Gq/11 protein family, triggering downstream signaling (phospholipase C activation, IP3 production, calcium release, and protein kinase C activation)[1][3]. In the brain, M3 may confer neuroprotective effects relevant to neurodegenerative disorders such as Alzheimer's disease[2]. M3 is a validated therapeutic target in asthma, COPD (bronchodilation), overactive bladder, irritable bowel syndrome, and several CNS conditions, with both approved drugs and investigational selective antagonists in clinical development[2][5][4]. However, lack of selectivity among muscarinic receptor subtypes introduces significant safety challenges and restricts broader application in non-localized therapies[5][4].

Other names

Cholinergic receptor, muscarinic 3CHRM3 (gene name)Muscarinic 3Muscarinic acetylcholine receptor M3

Antagonism: Many drugs inhibit M3 receptor activity, leading to relaxation of airway smooth muscle, reduced glandular secretion, or modulation of bladder contraction[5][4][7]. Modulation of Gq-coupled signal transduction: Activation leads to phospholipase C activation, increased inositol trisphosphate (IP3), and intracellular calcium signaling[1][3].