Autonomic receptors compared — muscarinic, nicotinic, adrenergic and dopamine
Verified · Oct 2026Acetylcholine acts on muscarinic receptors, which are G-protein-coupled, and on nicotinic receptors, which are ion channels. Norepinephrine and epinephrine act on α and β receptors, all G-protein-coupled. Knowing each receptor’s coupling and location predicts what its agonists and antagonists do.
Three G-protein pathways and two ion channels
Acetylcholine acts on muscarinic M1–M5 and nicotinic receptors. M1 and M3 couple to Gq: phospholipase C forms IP3 and DAG, and the rise in intracellular calcium drives smooth-muscle contraction and exocrine secretion. M2 couples to Gi, lowering cAMP; in the SA and AV nodes it opens potassium channels, hyperpolarizing the cells and slowing the heart. Nicotinic receptors are ligand-gated ion channels: at the neuromuscular junction acetylcholine opens them, sodium flows in, and the endplate depolarizes.
Adrenergic receptors are all G-protein-coupled. α1 receptors are Gq-coupled, like M3, and contract vascular smooth muscle; α2 receptors are Gi-coupled and, on nerve endings, inhibit norepinephrine release. All β receptors are Gs-coupled: adenylyl cyclase raises cAMP, which speeds and strengthens the heart through β1, relaxes bronchial and vascular smooth muscle through β2, and relaxes the detrusor through β3. Selectivity is relative — agonists and β1-selective blockers bind more receptor types at higher doses. Dopamine receptors split the same way: D1 is Gs-coupled and raises cAMP, while D2 is Gi-coupled, inhibiting adenylyl cyclase and opening potassium channels.
Comparison
Cholinergic receptors
| Receptor | Coupling | Second messenger or ion event | Main locations | Effect when stimulated | Example agonist | Example antagonist |
|---|---|---|---|---|---|---|
| M1 | Gq | Phospholipase C → IP3 + DAG → ↑ intracellular Ca²⁺ | CNS; gastric parietal cells | Cognition — learning and memory | Cholinesterase inhibitors act indirectly — donepezil, galantamine, rivastigmine in Alzheimer disease | Antimuscarinics that reach the CNS — blockade can cause confusion and cognitive impairment |
| M2 | Gi | ↓ adenylyl cyclase → ↓ cAMP; K⁺ efflux hyperpolarizes nodal cells | Heart — SA and AV nodes | Slower heart rate, less atrial contractility, slower AV conduction | Choline esters; cholinesterase inhibitors act indirectly (bradycardia) | Atropine — blocking M2 raises the heart rate |
| M3 | Gq | Phospholipase C → IP3 + DAG → ↑ Ca²⁺ (calmodulin → MLCK in smooth muscle) | GI, bladder, airway and eye smooth muscle; exocrine glands; vascular endothelium | Contraction (GI, detrusor, bronchi, iris sphincter); salivation, sweating, lacrimation; endothelial NO → vasodilation | Bethanechol, pilocarpine, cevimeline | Atropine, oxybutynin; darifenacin is M3-selective |
| M3 in the bladder | Gq | ↑ Ca²⁺ → calmodulin → MLCK | Detrusor (M2 is the more numerous subtype, but M3 mediates most contraction) | Detrusor contraction — voiding | Bethanechol | Darifenacin, solifenacin, tolterodine, trospium |
| Nn (ganglionic) | Ligand-gated ion channel | — | Autonomic ganglia, adrenal medulla, CNS | Ganglionic transmission; in excess, adrenal hypertension, sweating and tachycardia | Nicotine; succinylcholine also stimulates ganglia | Mecamylamine (ganglion blocker) |
| Nm (neuromuscular) | Ligand-gated ion channel | Na⁺ influx → endplate potential | Skeletal muscle endplate (junctional folds) | Muscle action potential and contraction; in excess, fasciculations then paralysis | Succinylcholine (depolarizing) | Rocuronium, vecuronium, cisatracurium (competitive) |
— = not stated on the source pages.
Adrenergic and dopamine receptors
| Receptor | Coupling | Second messenger | Main locations | Effect when stimulated | Example agonist | Example antagonist |
|---|---|---|---|---|---|---|
| α1 | Gq | Phospholipase C → IP3 + DAG → ↑ Ca²⁺ | Vascular smooth muscle; prostate, prostatic urethra and bladder neck | Vasoconstriction (↑ BP and resistance); mydriasis; bladder-neck contraction | Phenylephrine, midodrine | Tamsulosin, alfuzosin, silodosin (uroselective); phentolamine and phenoxybenzamine (nonselective) |
| α2 | Gi | Adenylate cyclase inhibited → ↓ cAMP | Peripheral nerve endings; brainstem | Inhibits further norepinephrine release (feedback); centrally, ↓ sympathetic outflow | Clonidine — acts centrally, lowering BP and heart rate | Phentolamine, phenoxybenzamine — more norepinephrine release, β stimulation and tachycardia |
| β1 | Gs | Adenylyl cyclase → ↑ cAMP → PKA | Heart (SA node, AV node, ventricles); kidney juxtaglomerular cells; adipocytes | ↑ Heart rate and contractility; renin release; lipolysis | Dobutamine (β1 > β2) | Metoprolol (β1-selective) |
| β2 | Gs | ↑ cAMP → PKA inactivates MLCK | Bronchial and vascular smooth muscle; uterus | Bronchodilation, vasodilation, glycogenolysis; tremor; uterine relaxation (tocolysis); K⁺ shift into cells (hypokalemia) | Epinephrine (low doses), isoproterenol; terbutaline (off-label, to delay preterm labor) | Propranolol (nonselective) |
| β3 | Gs | Adenylyl cyclase → ↑ cAMP | Detrusor | Detrusor relaxation during filling → ↑ bladder capacity | Mirabegron, vibegron | — |
| D1 | Gs | Adenylyl cyclase → ↑ cAMP → PKA | Renal, mesenteric and coronary vasculature | Vasodilation | Dopamine at low rates | — |
| D2 | Gi | Adenylyl cyclase inhibited; K⁺ channels open | CNS — striatum, nucleus accumbens, hippocampus, amygdala, cerebral cortex | Locomotion, attention, sleep, memory and learning | Bromocriptine; pramipexole, ropinirole | Haloperidol |
— = not stated on the source pages.
High-yield
Practice questions
Q1A 64-year-old woman with Sjögren syndrome takes a much larger dose of oral pilocarpine than prescribed. Within an hour she has pinpoint pupils, wheezing and drooling.
Through which receptor and pathway does pilocarpine produce these effects?
- A.M3 — Gq, with IP3 and DAG raising intracellular Ca²⁺
- B.β2 — Gs, with a rise in cAMP
- C.Nm — a ligand-gated Na⁺ channel
- D.α1 — Gq, with IP3 and DAG raising intracellular Ca²⁺
- E.M2 — Gi, with a fall in cAMP
Show answer
A. M3 — Gq, with IP3 and DAG raising intracellular Ca²⁺ — Pilocarpine is a direct muscarinic agonist. M3 receptors couple to Gq: phospholipase C forms IP3 and DAG, intracellular calcium rises, smooth muscle contracts — the iris sphincter (miosis) and bronchi — and exocrine glands secrete. β2 stimulation relaxes bronchial smooth muscle, and α1 stimulation causes mydriasis, not miosis. M2 receptors are in the SA and AV nodes, where they slow the heart, and Nm receptors are at the skeletal muscle endplate.
Q2A 70-year-old man with symptomatic sinus bradycardia receives IV atropine, and his heart rate rises.
Blockade of which receptor explains the rise in heart rate?
- A.β1 receptors in the SA node
- B.Nn receptors in autonomic ganglia
- C.M3 receptors on vascular smooth muscle
- D.M2 receptors in the SA and AV nodes
- E.α1 receptors on vascular smooth muscle
Show answer
D. M2 receptors in the SA and AV nodes — M2 receptors are found predominantly in the SA and AV nodal cells; through Gi they open potassium channels and slow the heart, so a muscarinic antagonist binding M2 increases the heart rate. Blocking β1 would slow the heart, since β1 stimulation raises the rate. Antimuscarinics cause minimal blockade at nicotinic sites, M3 receptors mediate smooth-muscle and gland effects rather than heart rate, and α1 receptors mediate vasoconstriction.
Q3A 68-year-old man with symptomatic bradycardia awaiting a pacemaker is started on an isoproterenol infusion. His heart rate rises, and he develops a fine tremor and feels anxious.
Stimulation of which receptor most likely causes his tremor?
- A.β1
- B.β2
- C.α1
- D.M2
- E.D1
Show answer
B. β2 — Isoproterenol is a nonselective β1 and β2 agonist with very low affinity for α receptors. Tremor, along with tachycardia, palpitations and anxiety, is a β2 effect; β1 stimulation causes tachycardia, palpitations and tachyarrhythmias. α1 stimulation constricts vessels, M2 stimulation slows the heart, and D1 stimulation dilates renal, mesenteric and coronary vessels.
Q4A 70-year-old woman with overactive bladder is started on mirabegron instead of an antimuscarinic.
Which intracellular event mediates mirabegron’s effect on the detrusor?
- A.IP3 and DAG formation with a rise in intracellular Ca²⁺
- B.Opening of a ligand-gated Na⁺ channel
- C.K⁺ efflux through Gi-activated channels
- D.Release of stored norepinephrine from nerve endings
- E.A rise in cAMP through Gs and adenylyl cyclase
Show answer
E. A rise in cAMP through Gs and adenylyl cyclase — Mirabegron is a β3 agonist: β3 stimulation activates adenylyl cyclase, cAMP rises, and the detrusor relaxes during filling, increasing bladder capacity. IP3, DAG and calcium are the Gq pathway of M3 and α1 receptors, which contracts smooth muscle; acetylcholine contracts the detrusor mainly through M3. Ligand-gated Na⁺ channels are nicotinic receptors, Gi-driven K⁺ efflux is how M2 slows the heart, and releasing norepinephrine is an indirect action, as with ephedrine, rather than mirabegron’s direct receptor agonism.
Sources
- Cholinergic Medications — StatPearls (NCBI)
- Muscarinic Antagonists — StatPearls (NCBI)
- Anticholinergic Toxicity — StatPearls (NCBI)
- Neuromuscular Blocking Agents — StatPearls (NCBI)
- Alpha-Blockers — StatPearls (NCBI)
- Adrenergic Drugs — StatPearls (NCBI)
- Muscarinic Agonists — StatPearls (NCBI)
- Cholinergic Crisis — StatPearls (NCBI)
- Physiology, Neuromuscular Transmission — StatPearls (NCBI)
- Depolarizing Neuromuscular Blocking Drugs — StatPearls (NCBI)
- Physiology, Bladder — StatPearls (NCBI)
- Current pharmacotherapy of overactive bladder (Int Braz J Urol, 2021) — PubMed Central
- MYRBETRIQ (mirabegron) — FDA label — FDA / DailyMed
- Isoproterenol — StatPearls (NCBI)
- Inotropes and Vasopressors — StatPearls (NCBI)
- Midodrine HCl Tablets — FDA label — FDA / DailyMed
- AKOVAZ (ephedrine sulfate injection) — FDA label — FDA / DailyMed
- Beta 1 Receptors — StatPearls (NCBI)
- Propranolol — StatPearls (NCBI)
- TOPROL-XL (metoprolol succinate) — FDA label — FDA / DailyMed
- Bethanechol Chloride Tablets — FDA label — FDA / DailyMed
- Oxybutynin Chloride Tablets — FDA label — FDA / DailyMed
- Physiology, Muscarinic Receptor — StatPearls (NCBI)
- Physiology, Cholinergic Receptors — StatPearls (NCBI)
- Biochemistry, Dopamine Receptors — StatPearls (NCBI)
- Beta2-Receptor Agonists and Antagonists — StatPearls (NCBI)
- Clonidine — StatPearls (NCBI)
- Beta2-Agonists — StatPearls (NCBI)
- VECAMYL (mecamylamine) — FDA label — FDA / DailyMed
- Haloperidol Decanoate Injection — FDA label — FDA / DailyMed
- Selective Beta-1 Blockers — Gs/cAMP signalling, PR interval, masked hypoglycemia, glucagon via Gαs — StatPearls (NCBI)
- Dopamine HCl Injection (Hospira) — FDA label — FDA / DailyMed
- Cholinesterase Inhibitors — anionic and esteratic sites, reversible vs irreversible, pharmacokinetics — StatPearls (NCBI)
- Tamsulosin Hydrochloride Capsules (Zydus) — FDA label — FDA / DailyMed
- Tenormin (atenolol) — clinical pharmacology, renal elimination (FDA label) — FDA / DailyMed
- Atropine Sulfate Injection — FDA label — FDA / DailyMed
- Organophosphate Toxicity — StatPearls (NCBI)
- Pilocarpine Ophthalmic Solution — ciliary-muscle mechanism, systemic exposure (FDA label) — FDA / DailyMed
- Oxytrol (oxybutynin transdermal) — CYP3A4 first pass, N-desethyloxybutynin ratio (FDA label) — FDA / DailyMed
- Darifenacin Extended-Release Tablets (Torrent) — M3 selectivity, CYP2D6 (FDA label) — FDA / DailyMed
- QUELICIN (succinylcholine chloride) — FDA label — FDA / DailyMed
- Rocuronium bromide injection — competitive mechanism, hepatic elimination (FDA label) — FDA / DailyMed
- Phenylephrine HCl Injection (Dr. Reddy’s) — FDA label — FDA / DailyMed
- Perioperative Management of Pheochromocytoma — α before β, labetalol — StatPearls (NCBI)
- CATAPRES-TTS (clonidine transdermal) — FDA label — FDA / DailyMed
- Beta Blockers — receptor subtypes, selective vs non-selective agents, α1 blockade, CNS effects — StatPearls (NCBI)
- Dobutamine — StatPearls (NCBI)
- ADRENALIN (epinephrine) — FDA label — FDA / DailyMed
- Isoproterenol HCl Injection (Amphastar) — FDA label — FDA / DailyMed
- GEMTESA (vibegron) — FDA label — FDA / DailyMed
- SALAGEN (pilocarpine) tablets — FDA label — FDA / DailyMed
- Transderm Scōp (scopolamine) — mechanism, blood–brain barrier, transdermal pharmacokinetics (FDA label) — FDA / DailyMed
- MESTINON (pyridostigmine) — FDA label — FDA / DailyMed
- Succinylcholine Chloride — receptor upregulation and hyperkalemia, bradycardia, BCHE/RYR1 — StatPearls (NCBI)
- Cisatracurium besylate injection — Hofmann elimination, laudanosine (FDA label) — FDA / DailyMed
- Phenylephrine — StatPearls (NCBI)
- Dobutamine Injection (Hospira) — FDA label — FDA / DailyMed
Each class page compared lists its full sources; this page reuses facts verified there.
By LearnDrugs
Educational summary for medical students. Always verify against current prescribing information and guidelines. Not medical advice.