Muscarinic acetylcholine receptor M1, Muscarinic acetylcholine receptor M3, Muscarinic acetylcholine receptor M5 (M1, M3, M5)

The muscarinic acetylcholine receptors M1, M3, and M5 are members of the GPCR superfamily and are activated by the neurotransmitter acetylcholine. These subtypes preferentially couple to Gq proteins, which activate phospholipase C and trigger downstream calcium signaling. M1, M3, and M5 play critical roles in both the central and peripheral nervous systems, mediating diverse physiological effects such as smooth muscle contraction, glandular secretion, vasodilation, cognition, and regulation of metabolic functions. Although these subtypes share high sequence homology, their tissue expression profiles and physiological roles differ. They are implicated in various diseases, from neurodegenerative disorders to metabolic and cardiovascular diseases. Drug development targeting these receptors faces the challenge of limited subtype-selectivity, leading to side effects when non-selective agents are used.

Other names

M1 receptorM3 receptorM5 receptorCHRM1CHRM3CHRM5 (human genes)Cholinergic receptor muscarinic M1M3M5

Agonists: Stimulate the receptor, leading to activation of the Gq/11 pathway, increased phospholipase C activity, inositol trisphosphate (IP3) and diacylglycerol (DAG) formation, and elevated intracellular calcium, which stimulates muscle contraction and glandular secretion. Antagonists: Block receptor function, reducing cholinergic signaling. Allosteric modulators: Bind and modify receptor response to acetylcholine.