CHRM4
Description
The CHRM4 (cholinergic receptor muscarinic 4) is a protein-coding gene located on chromosome 11.
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 ==
=== Orthosteric agonists === acetylcholine carbachol oxotremorine
=== Positive allosteric modulators === LY-2033298 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 Himbacine Mamba toxin 3 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) Diphenhydramine
== 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.
CHRM4 is also known as HM4, M4R.
