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. 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. ==Ligands==