Muscarinic receptors: what are they and what functions do they have?

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

Up to five different types of these receptors and the genes involved in their encoding have been identified. Next we will see a little more in depth where muscarinic receptors can be found and what functions they perform.

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What are muscarinic receptors?

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

They are called muscarinic because are more sensitive to muscarine than to nicotine, unlike its 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, activating them as selective agonists or antagonists.

Functions and location

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

In the brain, receptors of this type are found on synaptic terminals., regulating 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 fulfill the following functions.

1. recovery recipients

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

After this process, there is a hyperpolarization of the neuron, followed by a slow depolarization, which supposes a period of recovery for the postganglionic neuron. This process is mediated by the 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 acetylcholine is also found in this subsystem of the autonomous system.

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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 at 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 called "M" followed by a number between 1 and 5. M1, M3, and M5 receptors couple to Gq proteins, while M2 and M4 couple to Gi/o proteins.

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

1. M1 receiver

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

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2. M2 receiver

M2 receivers They 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 down the rate of depolarization.

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

3. M3 receiver

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

4. M4 receiver

The M4 receptor is found primarily in the central nervous system and has inhibitory functions. If they are stimulated with muscarinic agonists, bronchospasms can be caused.

5. M5 receiver

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

clinical significance

Different brain functions are known in which acetylcholine and its receptors, including muscarinic receptors, are involved. This can be observed in some pathologies, related to alterations in cholinergic transmission, The case of neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease is notable.

In 1976 the first biochemical abnormality associated with Alzheimer's disease was known. It was seen that in hippocampus and the cerebral cortex of the patients 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 acetylcoenzyme A.

Alzheimer disease

That there is less activity of the CAT indicates that it is taking place a loss of cholinergic nerve endings that release acetylcholine in brain regions which, once they degenerate, are associated with the symptoms of Alzheimer's. The regions with the greatest deficit are the Meynert's basal nucleus 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 preserves. 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 linked to the most well-known symptom of the disease: memory loss. Cholinergic terminals in the hippocampus are very important for memory formation and therefore the cognitive defects of the disease are related to problems in the function of muscarinic receptors in this region and the synthesis of the neurotransmitter.

Bibliographic references:

• Eglen RM (July 2006). "Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function". Autonomic & Autocoid 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.