Supriya Ghosh (Editor)

Muscarinic acetylcholine receptor M4

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Species
  
Human

Entrez
  
1132

Human
  
Mouse

Ensembl
  
ENSG00000180720

Muscarinic acetylcholine receptor M4

Aliases
  
CHRM4, HM4, M4R, cholinergic receptor muscarinic 4

External IDs
  
MGI: 88399 HomoloGene: 20192 GeneCards: CHRM4

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.

Contents

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.

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)
  • References

    Muscarinic acetylcholine receptor M4 Wikipedia