The muscarinic acetylcholine receptor M₄, also known as the cholinergic receptor, muscarinic 4 (CHRM4), is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that, in humans, is encoded by the ''CHRM4''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Function

M₄ muscarinic receptors are coupled to G_i/o heterotrimeric proteins. They function as inhibitory

autoreceptors An autoreceptor is a type of receptor located in the membranes of nerve cells. It serves as part of a negative feedback loop in signal transduction. It is only sensitive to the neurotransmitters or hormones released by the neuron on which the a ...

for acetylcholine. Activation of M₄ receptors inhibits

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

release in the

striatum The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives gluta ...

. The M₂ subtype of acetylcholine receptor functions similarly as an inhibitory autoreceptor to acetylcholine release, albeit functioning actively primarily in the

hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic syste ...

and

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...

. Muscarinic acetylcholine receptors possess a regulatory effect on

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate do ...

neurotransmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), ...

. Activation of M₄ receptors in the

inhibit D₁-induced

locomotor stimulation Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inappr ...

mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus'' ...

. M₄ receptor-deficient mice exhibit increased locomotor simulation in response to D₁ agonists,

amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

and

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...

. Neurotransmission in the striatum influences extrapyramidal

motor control Motor control is the regulation of movement in organisms that possess a nervous system. Motor control includes reflexes as well as directed movement. To control movement, the nervous system must integrate multimodal sensory information (both ...

, thus alterations in M₄ activity may contribute to conditions such as

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...

Ligands

Orthosteric agonists

carbachol Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a cholinomimetic drug that binds and activates acetylcholine receptors. Thus it is classified as a cholinergic agonist. It is primarily used for var ...

oxotremorine Oxotremorine is a drug that acts as a selective muscarinic acetylcholine receptor agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell ...

Positive allosteric modulators

* LY-2033298 * VU-0152100 (ML-108) * VU-0152099

Antagonists

AFDX-384 AFDX-384 (BIBN-161) is a drug which acts as a selective antagonist of the muscarinic acetylcholine receptors, with selectivity for the M2 and M4 subtypes. It is used mainly for mapping the distribution of M2 and M4 muscarinic receptors in the br ...

(mixed M2/M4 antagonist, N- -[2-[(Dipropylamino)methyl1-piperidinyl.html" ;"title="-[(Dipropylamino)methyl.html" ;"title="-[2-[(Dipropylamino)methyl">-[2-[(Dipropylamino)methyl1-piperidinyl">-[(Dipropylamino)methyl.html" ;"title="-[2-[(Dipropylamino)methyl">-[2-[(Dipropylamino)methyl1-piperidinylthyl]-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

,2-b The comma is a punctuation mark that appears in several variants in different languages. It has the same shape as an apostrophe or single closing quotation mark () in many typefaces, but it differs from them in being placed on the baseline ...

yrrolo

,2-f The comma is a punctuation mark that appears in several variants in different languages. It has the same shape as an apostrophe or single closing quotation mark () in many typefaces, but it differs from them in being placed on the baseline o ...

1,3]benzoxazine-1-carboxylic acid ethyl ester, CAS# 23062-91-1) *

PD-0298029 PD-0298029 is a drug which acts as a selective antagonist for the muscarinic acetylcholine receptor M4. It was developed for the treatment of Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative ...

Tropicamide Tropicamide, sold under the brand name Mydriacyl among others, is a medication used to dilate the pupil and help with examination of the eye. Specifically it is used to help examine the back of the eye. It is applied as eye drops. Effects occ ...

- moderate selectivity over other muscarinic subtypes (2-5x approx) *

Diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into ...

References

External links

* {{DEFAULTSORT:Muscarinic Acetylcholine Receptor M4 G protein-coupled receptors Human proteins Muscarinic acetylcholine receptors