Muscarinic acetylcholine receptors (mAChR)

[WG21:p101-103]

• Stimulated by muscarine (toxic alkaloid in toadstools)
• Blocked by atropine
• 5 different subtypes
  * M1-M4 are all G-protein-coupled receptors
  * M5 is uncertain
• M1 is abundant in brain
• M2 is found in heart
  * Decreased cAMP --> Decreased Ca2+ conductance and increased K+ conductance [RD5:p139]
• M3 is found in smooth muscles
  * Increased IP3 --> Increased intracellular Ca2+ [RD5:p139]
• M4 is found in smooth muscles and pancreatic acinar and islet tissues
  --> Mediates secretion of pancreatic enzymes and insulin

According to [SH4:p266-p267]

• M1 = CNS and stomach
  --> Inhibition causes decrease in gastric acid secretion
• M2 = Heart, CNS, airway smooth muscles
  --> Inhibition causes bradycardia
• M3 = CNS, airway smooth muscles, glandular tissues, vascular endothelial cells
  --> Inhibition causes bronchodilation, vasodilation, and antisialogogue effect
• M4 = CNS and heart
• M5 = CNS
• M1, M3, and M5 activate G proteins
  --> Phospholipase C stimulation and Ca2+ release
• M2 and M4 activate G proteins
  --> Inhibition of adenylyl cyclase and inhition of voltage-sensitive Ca2+ channels

NB:

• M1, M3, M5 stimulates phopholipase C via G protein
  * [SH4:p266; RD5:p139]
  * c.f. M1, M4, M5 [WG21:p99]
• M2, M4 inhibits adenylyl cyclase
  * [SH4:p267; RD5:p139]
  * c.f. M2, M3 [WG21:p99]