muscarinergic

Muscarinergic refers to the actions and receptors mediated by acetylcholine at muscarinic acetylcholine receptors (mAChRs). The term derives from muscarine, a toxin found in certain mushrooms that selectively activates these receptors, and is used to distinguish muscarinic signaling from nicotinic cholinergic signaling.

Muscarinic receptors are a family of G protein–coupled receptors divided into five subtypes, M1 through M5. They are widely distributed in the central nervous system and in peripheral tissues, where they regulate parasympathetic responses. Different subtypes couple to distinct G proteins and signaling pathways, with M1, M3, and M5 typically activating phospholipase C via Gq/11, and M2 and M4 primarily inhibiting adenylate cyclase via Gi/o. This diversity underpins a range of effects, including modulation of cognitive function in the brain and control of heart rate, smooth muscle tone, and glandular secretion in the periphery.

Pharmacologically, muscarinergic activity is driven by endogenous acetylcholine and can be influenced by agonists such as bethanechol or pilocarpine, which mimic acetylcholine at mAChRs, or by antagonists such as atropine and scopolamine, which block receptor activation. Toxicology discussions often emphasize organophosphate poisoning, where excessive acetylcholine stimulates muscarinic and nicotinic receptors; treatment commonly involves atropine to counteract muscarinic effects.

In research and medicine, muscarinergic signaling is studied for its roles in learning and memory, sensory processing, and autonomic regulation, as well as for its therapeutic potential in disorders ranging from gastrointestinal hypomotility to glaucoma and certain neurodegenerative diseases.