Muscarinic acetylcholine receptor M4 (IPR001432)

Short name: Musac_Ach_M4_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].

The muscarinic acetylcholine M4 receptor is primarily found in the CNS [PMID: 2402490, PMID: 8429821, PMID: 7751967], its distribution largely overlapping with that of M1 and M3 subtypes. M4 receptors function as inhibitory autoreceptors for acetylcholine [PMID: 9353395, PMID: 10711347], activation of which inhibits acetylcholine release in the striatum.

Muscarinic acetylcholine receptors possess a regulatory effect on dopaminergic neurotransmission and activation of M4 receptors in the striatum inhibits dopamine-induced locomotor stimulation in mice [PMID: 12144929]. M4 receptor-deficient mice exhibit increased locomotor simulation in response to dopamine agonists, such as amphetamine and cocaine [PMID: 10468635, PMID: 20147565, PMID: 21373792, PMID: 17762886]. Neurotransmission in the striatum influences extrapyramidal motor control. Therefore, alterations in M4 receptor activity may contribute to conditions such as Parkinson's Disease [PMID: 18082893, PMID: 20551968, PMID: 21113197].

GO terms

Biological Process

GO:0007186 G protein-coupled receptor signaling pathway
GO:0040012 regulation of locomotion

Molecular Function

GO:0016907 G protein-coupled acetylcholine receptor activity

Cellular Component

GO:0005887 integral component of plasma membrane

Contributing signatures

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