CHRM3

CHRM3, or cholinergic receptor, muscarinic 3 (M3), is a human gene that encodes the muscarinic acetylcholine receptor M3, a seven-transmembrane G protein-coupled receptor in the M1–M5 family.

The M3 receptor is activated by acetylcholine and couples primarily to heterotrimeric G proteins of the Gq/11 family, leading to phospholipase C activation, inositol trisphosphate and diacylglycerol production, and a rise in intracellular calcium. This signaling promotes contraction of smooth muscle and stimulation of glandular secretion. It also mediates nitric oxide release in vascular endothelium, contributing to vasodilation.

Expression of the M3 receptor is widespread in tissues including smooth muscle cells of the airway, gastrointestinal tract, and urinary bladder, as well as various exocrine glands such as the salivary glands. In the eye, the receptor mediates pupil constriction by acting on the iris sphincter muscle and influences ciliary muscle function. In the central nervous system, M3 receptors are present in certain brain regions and have been implicated in cognitive and autonomic processes.

Clinical relevance involves the receptor’s role in bronchoconstriction and glandular secretion. Pharmacologically, antagonists that block M3 activity are used to treat conditions such as overactive bladder (examples include oxybutynin and darifenacin, with darifenacin exhibiting relative M3 selectivity) and can help mitigate some respiratory symptoms. Adverse effects of antimuscarinic therapies often include dry mouth, constipation, and blurred vision due to broad muscarinic blockade.

CHRM3 is one member of the muscarinic receptor gene family within the G protein-coupled receptor superfamily, and it remains a focus of research for understanding autonomic regulation and drug development.