Autonomic Nervous System Series  ·  Module 3

Autonomic Receptors: Classification, Signaling, and Tissue Distribution

Muscarinic, nicotinic, and adrenergic receptor subtypes — G-protein coupling, tissue locations, and key drugs

Muscarinic Receptors (G-Protein-Coupled)

Subtype G-Protein Primary Location Effect of Activation Key Drugs
M1GqCNS neurons, autonomic gangliaCognitive facilitation; gastric acid secretionPirenzepine (antagonist, peptic ulcer — limited use)
M2GiHeart (SA/AV nodes)Bradycardia, slowed AV conductionAtropine (antagonist — raises heart rate)
M3GqSmooth muscle, glands, iris sphincterBronchoconstriction, secretion, miosis, bladder contractionPilocarpine (agonist — glaucoma); tiotropium, ipratropium (antagonist — chronic obstructive pulmonary disease)
M4GiCNS striatumDopaminergic modulationXanomeline-trospium (M1/M4 — schizophrenia)
M5GqCNS (limited)Dopaminergic neuron modulationNo selective clinical drugs currently

Nicotinic Receptors (Ligand-Gated Ion Channels)

N-N Subtype

Ganglionic Nicotinic

LocationAll autonomic ganglia; adrenal medulla chromaffin cells
EffectDepolarizes postganglionic neuron; triggers catecholamine release from adrenal medulla
AgonistNicotine (low dose); acetylcholine
AntagonistTrimethaphan, mecamylamine — bilateral autonomic blockade

N-M Subtype

Neuromuscular Nicotinic

LocationSkeletal muscle motor endplate only
EffectEndplate depolarization → skeletal muscle contraction
AgonistSuccinylcholine (depolarizing blocker — paralysis by sustained depolarization)
AntagonistRocuronium, vecuronium (non-depolarizing — reversed by neostigmine/sugammadex)

Adrenergic Receptors (G-Protein-Coupled)

Subtype G-Protein Primary Location Effect of Activation Key Drugs
α1GqVascular smooth muscle, iris dilator, prostateVasoconstriction, mydriasis, urethral contractionPhenylephrine (agonist); prazosin, tamsulosin (antagonist)
α2GiPresynaptic terminals; CNS; plateletsReduces NE release; central sympatholysis; platelet aggregationClonidine (agonist — antihypertensive); yohimbine (antagonist)
β1GsHeart (SA/AV/ventricle); kidney (JG cells)Increased rate, conduction, contractility; renin releaseDobutamine (agonist); metoprolol, atenolol (selective antagonist)
β2GsBronchial smooth muscle; skeletal muscle vessels; uterusBronchodilation; vasodilation; uterine relaxationAlbuterol, salmeterol (agonist — asthma); terbutaline (tocolytic)
β3GsAdipose; bladder detrusorLipolysis; bladder relaxationMirabegron (agonist — overactive bladder)

Receptor Regulation

Process 1

Desensitization

Minutes. G-protein-coupled receptor kinase phosphorylates receptor → arrestin binds → uncouples from G-protein. Receptor surface, not signaling. Reversible.

Process 2

Downregulation

Hours to days. Receptor internalized into endosomes → degraded or recycled. Net loss of surface receptors. Clinical example: beta-2 agonist tolerance with overuse.

Process 3

Upregulation

Chronic antagonist blockade → compensatory increase in receptor number. Abrupt beta-blocker withdrawal → rebound tachycardia from upregulated beta-1 receptors. Always taper.