Muscarinic acetylcholine receptor M2 (IPR001065)

Short name: Musac_Ach_M2_rcpt

Overlapping homologous superfamilies


Family relationships


Muscarinic acetylcholine receptors are members of rhodopsin-like G-protein coupled receptor family. They play several important roles; they mediate many of the effects of acetylcholine in the central and peripheral nervous system and modulate a variety of physiological functions, such as airway, eye and intestinal smooth muscle contraction, heart rate and glandular secretions. The receptors have a widespread tissue distribution and are a major drug target in human disease. They may be effective therapeutic targets in Alzheimer's disease, schizophrenia, Parkinson's disease and chronic obstructive pulmonary disease [PMID: 15850824, PMID: 17762886].

There are five muscarinic acetylcholine receptor subtypes, designated M1-5 [PMID: 3443095, PMID: 3272174, PMID: 3037705, PMID: 9647869, PMID: 2470172]. The family can be further divided into two broad groups based on their primary coupling to G-proteins. M2 and M4 receptors couple to the pertussis-toxin sensitive Gi proteins, whereas M1, M3 and M5 receptors couple to Gq proteins [PMID: 9647869, PMID: 8853955], which activate phospholipase C. The different subtypes can also couple to a wide range of diverse signalling pathways, some of which are G protein-independent [PMID: 10841527, PMID: 14641022, PMID: 12725869]. All subtypes seem to serve as autoreceptors [PMID: 11714883], and knockout mice reveal the important neuromodulatory role played by this receptor family [PMID: 14744253, PMID: 15474550, PMID: 17762886].

Muscarinic acetylcholine receptor M2 is highly expressed in the heart and has a profound role in the control of myocyte contraction [PMID: 14744253, PMID: 7504306, PMID: 10581327]. The release of acetylcholine from vagal parasympathetic neurones reduces the heart beating frequency by acting almost exclusively at M2 muscarinic receptors [PMID: 9647869, PMID: 7504306, PMID: 10581327]. The M2 receptor is found at much lower levels in the CNS, where it has limited distribution [PMID: 3753655]. It is co-expressed with the M3 muscarinic receptors in smooth muscle [PMID: 8981565] and it appears to play a much smaller role in the smooth muscle contractile response [PMID: 14744253]. M2 receptors are also expressed in the thermo-regulatory centres of the hypothalamus and are likely to be involved in the regulation of body temperature [PMID: 9990086].

GO terms

Biological Process

GO:0007186 G protein-coupled receptor signaling pathway
GO:0008016 regulation of heart contraction

Molecular Function

GO:0016907 G protein-coupled acetylcholine receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.