Molecular properties of muscarinic acetylcholine receptors

Proc Jpn Acad Ser B Phys Biol Sci. 2013;89(6):226-56. doi: 10.2183/pjab.89.226.


Muscarinic acetylcholine receptors, which comprise five subtypes (M1-M5 receptors), are expressed in both the CNS and PNS (particularly the target organs of parasympathetic neurons). M1-M5 receptors are integral membrane proteins with seven transmembrane segments, bind with acetylcholine (ACh) in the extracellular phase, and thereafter interact with and activate GTP-binding regulatory proteins (G proteins) in the intracellular phase: M1, M3, and M5 receptors interact with Gq-type G proteins, and M2 and M4 receptors with Gi/Go-type G proteins. Activated G proteins initiate a number of intracellular signal transduction systems. Agonist-bound muscarinic receptors are phosphorylated by G protein-coupled receptor kinases, which initiate their desensitization through uncoupling from G proteins, receptor internalization, and receptor breakdown (down regulation). Recently the crystal structures of M2 and M3 receptors were determined and are expected to contribute to the development of drugs targeted to muscarinic receptors. This paper summarizes the molecular properties of muscarinic receptors with reference to the historical background and bias to studies performed in our laboratories.

Publication types

  • Review

MeSH terms

  • Acetylcholine / chemistry
  • Acetylcholine / metabolism
  • Animals
  • Central Nervous System / metabolism
  • Crystallography, X-Ray
  • G-Protein-Coupled Receptor Kinases / chemistry
  • G-Protein-Coupled Receptor Kinases / metabolism
  • GTP-Binding Protein alpha Subunits, Gi-Go / chemistry
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • GTP-Binding Protein alpha Subunits, Gq-G11 / chemistry
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Humans
  • Parasympathetic Nervous System / metabolism
  • Phosphorylation / physiology
  • Receptors, Muscarinic / chemistry*
  • Receptors, Muscarinic / metabolism*
  • Signal Transduction / physiology
  • Structure-Activity Relationship


  • Receptors, Muscarinic
  • G-Protein-Coupled Receptor Kinases
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Acetylcholine