Muscarinic acetylcholine receptor M4

M₄ muscarinic receptors are coupled to G_i/o heterotrimeric proteins.^[7]

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.^[8][9][10] Neurotransmission in the striatum influences extrapyramidal motor control, thus alterations in M₄ activity may contribute to conditions such as Parkinson's disease.^[11][12][13]

The M₄ muscarinic receptor has been found to be a regulator of erythroid progenitor cell differentiation. Inhibition of the M₄ muscarinic receptor provides therapeutic benefits in myelodysplastic syndrome and anemia.^[14][15][16]

• Muscarinic acetylcholine receptor