Muscarinic receptors: what are they and what are their functions?

This type of receptor is distributed throughout various organs and parts of the nervous system.

Muscarinic receptors are acetylcholine-sensitive receptors that have been linked to various neurodegenerative diseases, especially Alzheimer's and Parkinson's disease.

Up to five different types of these receptors and the genes involved in their coding have been identified. Below we will take a closer look at where muscarinic receptors can be found and what functions they perform.

What are muscarinic receptors?

Muscarinic receptors are acetylcholine receptors that form complexes with G proteins in the membranes of certain neurons. proteins in the membranes of certain neurons and other cells of the nervous system. They have several functions, being the main receptors stimulated by acetylcholine released by postganglionic fibers in the parasympathetic nervous system.

They are called muscarinic because they are more sensitive to muscarine than to nicotineUnlike their counterpart nicotinic receptors, which are very important in the autonomic nervous system. Many substances, such as scopolamine and pilocarpine, influence these two types of receptors by activating them as selective agonists or antagonists.

Functions and localization

Muscarinic receptors are found in various locations in the body, both organs and tissues, and within the central nervous system. Among the most notable tissues where these receptors can be found are smooth muscle and cardiac tissue, as well as some exocrine glands.

In the brain, receptors of this type are found in synaptic terminals, regulating the release of neurotransmitters, both from their own receptors and those of other neurons.They regulate the release of neurotransmitters, both from their own receptors and those of other neurons.

Acetylcholine is a neurotransmitter that can be found in the brain, although it is also found in other parts of the body such as neuromuscular junctions and ganglia. In the case of muscarinic receptors, they have the following functions.

1. Recovery receptors

Acetylcholine is always used as the neurotransmitter within the autonomic ganglion.. The nicotinic receptors of the postganglionic neuron are responsible for the initial rapid depolarization of the neuron.

After this process, there is a hyperpolarization of the neuron, followed by a slow depolarization, which is a period of recovery for the postganglionic neuron. This process is mediated by M1 and M2 muscarinic receptors.

2. Postganglionic neurons

Muscarinic receptors are present at the junction of innervated tissues and postganglionic neurons of the parasympathetic system, since this subsystem of the autonomic system also contains acetylcholine acetylcholine.They are also found in this subsystem of the autonomic system, since acetylcholine is also found in this subsystem.

3. Innervated tissue

Some parts of the sympathetic system use cholinergic receptors. This is the case of the sweat glands, whose receptors are of the muscarinic type.

In the somatic nervous system, nicotinic receptors for acetylcholine are used in the neuromuscular junctions.

Types of muscarinic receptors

Muscarinic receptors belong to the group of metabotropic receptors that use G proteins as a signaling mechanism. In these receptors, the molecule or ligand used to give the signal binds to the receptor, which has seven transmembrane regions. In the case of muscarinic receptors, the ligand is acetylcholine.

Up to five different types of muscarinic receptors have been discovered, which are named "M" followed by a number between 1 and 5. M1, M3 and M5 receptors are coupled to Gq proteins, while M2 and M4 are coupled to Gi/o proteins.

Studying chromosomes, geneticists and molecular biologists have discovered five genes that are involved in the coding of muscarinic receptors, being named in the same way as the Gq receptors.They are named in the same way as the receptors but with the letter "m" in lower case. Genes m1, m2, m3 and m4 encode for M-muscarinic receptors 1 to 4. M5 is a type of receptor subtype that has not yet been detected pharmacologically.

M1 receptor

This receptor is found mediating the slow excitatory postsynaptic potential (ESPS) of the ganglion in the postganglionic nerve. It is common in exocrine glands and in the central nervous system. It is mostly bound to Gq-type proteins.

M2 receptor

M2 receptors are found in the heart, where they are responsible for slowing down the heartbeat, keeping it below the normal rhythm.. They do this by slowing the rate of depolarization.

In humans, when we are resting, vagal activity dominates sympathetic activity. If M2 receptors are inhibited, then the heartbeat increases.

3. M3 receptor

The M3 receptor can be found in several places in the body. They are found in the muscles responsible for the contraction of the Blood capillaries and also in the lungs.. As with M1 receptors, M3 receptors are Gq-type proteins.

4. M4 receptor

The M4 receptor is found primarily in the central nervous system and has inhibitory functions. has inhibitory functions. If stimulated with muscarinic agonists, bronchospasm can occur.

5. M5 Receptor

The location of the M5 receptors is not fully known. As with M1 and M3 receptors, M5 is coupled to Gq proteins.

Clinical significance

Different brain functions are known in which acetylcholine and its receptors, including muscarinic receptors, are involved. This is possible to observe in some pathologies, related to alterations in cholinergic transmission, being remarkable the case of neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease.

In 1976 the first biochemical anomaly associated with Alzheimer's disease was discovered. It was found that in the hippocampus and cerebral cortex of the patients, the enzyme choline acetyltransferase (CAT) the enzyme choline acetyltransferase (CAT) was present at levels well below normal.. This enzyme catalyzes the synthesis of acetylcholine from its precursor substances: choline and acetyl coenzyme A.

Alzheimer's disease

The lower activity of CAT indicates that there is a loss of nerve terminals in the brain. a loss of cholinergic nerve terminals that release acetylcholine in brain regions, which, once they degenerate which, once they degenerate, are associated with the symptoms of Alzheimer's disease. The regions of greatest deficit are the nucleus basalis of Meynert and the temporal lobes.

In the case of this particular disease, the M2 receptor and nicotinic receptors, which are also sensitive to acetylcholine, are altered, while M1, which is present in the hippocampus, is more or less preserved. Other neurotransmitters are also involved in Alzheimer's disease, such as serotonin, glutamate, GABA, norepinephrine and somatostatin.

Biochemical abnormalities with respect to acetylcholine in the hippocampus have been related to the best known symptom of the disease: memory loss. The cholinergic terminals of the hippocampus are very important for memory formation and, therefore, the cognitive defects of the disease, the cognitive defects of the disease are related to problems in the function of muscarinic receptors in this region and the synthesis of the in this region and neurotransmitter synthesis.

Bibliographic references:

• Eglen RM (July 2006). "Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function". Autonomic & Autacoid Pharmacology. 26 (3): 219-33. doi:10.1111/j.1474-8673.2006.00368.x.
• Ishii M, Kurachi Y (2006). "Muscarinic acetylcholine receptors". Current Pharmaceutical Design. 12 (28): 3573–81. doi:10.2174/138161206778522056.
• Caulfield MP, Birdsall NJ (June 1998). "International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors". Pharmacological Reviews. 50 (2): 279–90.