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.

(Communicated by Masanori OTSUKA, M.J.A.)