The muscarinic acetylcholine receptor M<sub>4</sub>, also known as the cholinergic receptor, muscarinic 4 (CHRM4), is a protein that, in humans, is encoded by the CHRM4 gene.
M<sub>4</sub> muscarinic receptors are coupled to G<sub>i/o</sub> heterotrimeric proteins.
They function as inhibitory autoreceptors for acetylcholine. Activation of M<sub>4</sub> receptors inhibits acetylcholine release in the striatum. The M<sub>2</sub> 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 M<sub>4</sub> receptors in the striatum inhibit D<sub>1</sub>-induced locomotor stimulation in mice. M<sub>4</sub> receptor-deficient mice exhibit increased locomotor simulation in response to D<sub>1</sub> agonists, amphetamine and cocaine. Neurotransmission in the striatum influences extrapyramidal motor control, thus alterations in M<sub>4</sub> activity may contribute to conditions such as Parkinson's disease.
The M<sub>4</sub> muscarinic receptor has been found to be a regulator of erythroid progenitor cell differentiation. Inhibition of the M<sub>4</sub> muscarinic receptor provides therapeutic benefits in myelodysplastic syndrome and anemia.