Learning Objective
Describe the locations, receptor subtypes (M₁, M₂, M₃), and physiologic responses associated with muscarinic receptor activation across major organ systems.
Core Mechanisms
| Receptor |
G-protein |
Mechanism |
Result |
| M₁ |
Gq |
↑ IP₃/DAG → ↑ Ca²⁺ |
CNS/ENS activation, ↑ secretion |
| M₂ |
Gi |
↓ cAMP |
↓ HR, ↓ conduction |
| M₃ |
Gq |
↑ IP₃/DAG → ↑ Ca²⁺ |
Smooth muscle contraction, ↑ gland secretion |
Organ System Effects
1. Eye (M₃)
- Sphincter contraction → miosis
- Ciliary muscle contraction → near vision accommodation
2. Heart (M₂)
- SA node: ↓ HR (negative chronotropy)
- AV node: ↓ conduction velocity (negative dromotropy)
- No effect on ventricles or Purkinje fibers
3. Lungs (M₃)
- Bronchoconstriction
- ↑ bronchial secretions
4. GI Tract
| Target |
Receptor |
Effect |
| Stomach motility |
M₃ |
↑ motility → cramps |
| GI glands |
M₁ |
↑ secretion |
| Intestines |
M₃ |
Contraction → diarrhea, defecation |
5. Bladder (M₃)
- Detrusor contraction
- Trigone & sphincter relaxation
→ promotes urination and incontinence
6. Sphincters (M₃)
- Relaxation
- Exception: Lower esophageal sphincter contracts
7. Glands (M₃)
- ↑ sweat (thermoregulatory)
- ↑ salivation
- ↑ lacrimation
8. Blood Vessels (Endothelium Only) – M₃
- Vasodilation via NO
- No direct innervation → indirect agonists have no effect
Nicotinic Receptors
Nₙ (Neuronal)
- Autonomic ganglia → ganglionic stimulation
- Adrenal medulla → ↑ Epi & NE release
Nₘ (Muscle)
- NMJ → depolarization, skeletal muscle contraction
- Rapid desensitization with overstimulation
Mechanism Summary Table (Must-Know)
| Receptor |
Mechanism |
| M₁, M₃ |
Gq → ↑ IP₃/DAG → ↑ Ca²⁺ |
| M₂ |
Gi → ↓ cAMP |
| Nₙ, Nₘ |
Na⁺/K⁺ ion channel depolarization |
Activity
