Muscarinic

Muscarinic receptors are a family of acetylcholine receptors that mediate many parasympathetic nervous system effects. Unlike nicotinic receptors, they are G protein-coupled receptors (GPCRs) activated by acetylcholine and the alkaloid muscarine. In vertebrates there are five subtypes, M1 through M5, with distinct tissue distributions and signaling profiles.

Signaling and distribution vary by subtype: M1, M3, and M5 couple to Gq/11, activating phospholipase C and increasing intracellular Ca2+. M2 and M4 couple to Gi/o, inhibiting adenylyl cyclase and lowering cAMP, often affecting heart rate and neuronal excitability. M1 is prominent in the central nervous system and autonomic ganglia; M2 in the heart; M3 in smooth muscle and exocrine glands; M4 and M5 mainly in the brain.

Pharmacology and physiology: Endogenous acetylcholine activates all muscarinic receptors. Agonists such as bethanechol and pilocarpine mimic acetylcholine; antagonists such as atropine, scopolamine, ipratropium, and tiotropium block receptor activity. Muscarinic signaling modulates pupil constriction, accommodation, salivation, bronchoconstriction, gut motility, and bladder contraction. Clinically, muscarinic agents treat dry mouth, glaucoma, and certain motility disorders; antagonists are used for bradycardia, COPD, overactive bladder, and preanesthesia.

Selective ligands exist for certain subtypes (for example, M1-selective antagonists), but many drugs act nonselectively or with subtype bias. The concept of muscarinic receptors helps explain many physiological responses to acetylcholine and guides therapies across ophthalmology, urology, pulmonology, and neurology.