• Source: Muscarinic acetylcholine receptor M4

The muscarinic acetylcholine receptor M4, also known as the cholinergic receptor, muscarinic 4 (CHRM4), is a protein that, in humans, is encoded by the CHRM4 gene.




Function


M4 muscarinic receptors are coupled to Gi/o heterotrimeric proteins.
They function as inhibitory autoreceptors for acetylcholine. Activation of M4 receptors inhibits acetylcholine release in the striatum. The M2 subtype of acetylcholine receptor functions similarly as an inhibitory autoreceptor to acetylcholine release, albeit functioning actively primarily in the hippocampus and cerebral cortex.
Muscarinic acetylcholine receptors possess a regulatory effect on dopaminergic neurotransmission. Activation of M4 receptors in the striatum inhibit D1-induced locomotor stimulation in mice. M4 receptor-deficient mice exhibit increased locomotor simulation in response to D1 agonists, amphetamine and cocaine. Neurotransmission in the striatum influences extrapyramidal motor control, thus alterations in M4 activity may contribute to conditions such as Parkinson's disease.




Ligands






= Agonists

=
Acetylcholine
Carbachol
CMI-936
NBI-1117568 (HTL-0016878)
ML-007
Oxotremorine
Xanomeline




= Positive allosteric modulators

=
Emraclidine (CVL-231, PF-06852231)
LY-2033298
NS-136
SUVN-L3307032
VU-0152100 (ML-108)
VU-0152099




= Antagonists

=
AFDX-384 (mixed M2/M4 antagonist, N-[2-[2-[(Dipropylamino)methyl]-1-piperidinyl]ethyl]-5,6-dihydro-6-oxo-11H-pyrido[2,3-b][1,4]benzodiazepine-11-carboxamide, CAS# 118290-27-0)
Dicycloverine
Diphenhydramine
Himbacine
Mamba toxin 3
NBI-1076968
PD-102,807 (3,6a,11,14-Tetrahydro-9-methoxy-2-methyl-(12H)-isoquino[1,2-b]pyrrolo[3,2-f][1,3]benzoxazine-1-carboxylic acid ethyl ester, CAS# 23062-91-1)
PD-0298029
Tropicamide - moderate selectivity over other muscarinic subtypes (2-5x approx)




See also


Muscarinic acetylcholine receptor




References






Further reading






External links


Overview of all the structural information available in the PDB for UniProt: P08173 (Muscarinic acetylcholine receptor M4) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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