Acetylcholine

What's this? / Definition

Acetylcholine is one of the most important neurotransmitters both in humans and in numerous other organisms. In fact, acetylcholine already occurs in protozoa and is considered to be a very old substance in terms of evolutionary history. At the same time, it is the longest known neurotransmitter (it was first demonstrated experimentally in 1921), which is one of the reasons why it has been studied very intensively to this day.

Acetylcholine (abbreviated Oh) chemically belongs to the group of biogenic amines and plays both in central as well as in peripheral as well as the autonomic nervous system an enormously important role. However, it is best known for its function as a transmitter on the motor end plate (neuromuscular endplate), where it mediates the voluntary contraction of skeletal muscles.

Its role in the Learning process and the Training of memory. That being said, it is considered certain that he was involved in the emergence of the Sensation of pain and Maintaining our day-night rhythm, as well as at the Control of motor functions in the brain is involved. In addition, acetylcholine not only acts as a messenger substance in the Nervous system, but also as Hormone in the bloodstream and is here at the Regulation of heart rate and blood pressure involved.

Effects of acetylcholine

Since acetylcholine is one of the most widespread messenger substances in the human body, its effect on the organism is very extensive. Especially in its function as important neurotransmitter of all major nervous systems, ACh has a variety of tasks. On the neuromuscular endplate, it serves, among other things, to transmit excitation from the nerves to the muscle by binding to the nicotinic acetylcholine receptor, which causes it to Contraction of the muscle comes.

It is also an essential part of the conduction of excitation in the autonomic nervous system. Here acetylcholine transmits impulses from the first to the second neuron both in the parasympathetic (Parasympathetic nervous system), as well as the sympathetic System (Sympathetic). On the other hand, in the case of the parasympathetic nervous system, it is also responsible for connecting the second neuron to the respective target organ. The vegetative or autonomic nervous system is responsible for all involuntary functions of the internal organs. The parasympathetic nervous system in particular takes care of you Resting metabolism. In relation to the effect of acetylcholine, this ultimately means a slowing down of the heart rate and blood pressure, a narrowing of the bronchi, stimulation of digestion and functions such as increased salivation and constriction of the pupils.

In the central nervous system, on the other hand, there are many cognitive functions in connection. Among other things, it is involved in learning processes, the formation of memory and probably also in the development of drive. This is due to the consequences of the Alzheimer's disease can be seen in which it is mainly the sinking of Neurons which acetylcholine produce. In addition, as a hormone in the bloodstream, ACh has an effect on our circulatory system. Here it has a lowering effect on blood pressure, primarily by widening the blood vessels distant from the body.

Acetylcholine on the heart

As early as 1921, it was established that a chemical substance must be present which is responsible for the annoy transmitted electrical impulse to the heart. This substance was initially called vagus substance after the nerve whose impulse it mediates. It was later renamed acetylcholine instead, chemically correct. The Vagus nerve, with its messenger substance acetylcholine, is an important extension of the parasympathetic nervous system, which, in addition to the sympathetic nervous system, belongs to the vegetative or nervous system. This is responsible for controlling the involuntary body functions, such as digestion. The parasympathetic nerves in particular ensure a resting or recreational metabolism, thus promoting digestion, among other things. The sympathetic forms the opponent.

Acetylcholine also has a relaxing effect on the heart. The result is a slower heart rate and lower blood pressure. The docking point responsible for ACh is the M2 receptor, a so-called muscarinic receptor. You make use of this knowledge by taking part Atropine a drug was developed that blocks this receptor and thus counteracts the effect of the parasympathetic nervous system. This effect is called parasympatholytic. Atropine is used, for example, in emergency medicine. Another effect of acetylcholine on the circulatory system, again in line with the function of the parasympathetic nervous system, is for a Relaxation of the vascular muscles to care. This also results in a decrease in blood pressure.

Synapse

A synapse is a neural connection point between a neuron and another cell (usually another neuron, but often also a muscle, sensory or glandular cell). They serve the Transmission and partly the change of excitations, as well as the Storage of information by adapting the structure of the synapse. Humans have around 100 trillion synapses. A single neuron can have up to 200,000 synapses.

The transmission of the electrical signal from one synapse to a second is usually done chemically Neurotransmitters, also acetylcholine, which should serve as an example here. If an electrical signal reaches the synapse of neuron A, this leads to the release of acetylcholine from its storage locations within the synapse, the vesicles, in the synaptic cleft. This is microscopic in size, only around 20 to 30 nanometers wide. The acetylcholine then diffuses to the synapse of neuron B and docks here to special receptors. This in turn leads to the formation of an electrical impulse in neuron B, which is then passed on. After a short time, ACh is broken down by the enzyme acetylcholinesterase and rendered ineffective. Its components choline and acetic acid are then taken up again into the synapse of neuron A, so that acetylcholine can be formed again.

Besides these chemical synapses also exist electrical synapseswhich with Ion channels through which ions and small molecules can get from one cell to another. The electrical impulse can be transmitted directly between two or more cells.

Acetylcholine receptor

The neurotransmitter acetylcholine unfolds its effect via various receptors, which are built into the membrane of the corresponding cells. Since some of them also by nicotine When stimulated, they are known as nicotinic acetylcholine receptors. Another class of acetylcholine receptors is represented by the Toadstool poison (Muscarin) stimulated The term muscarinic is derived from this.

Muscarinic acetylcholine receptors

Muscarinic acetylcholine receptors (mAChR) belong to the group of G protein coupled receptors and can be divided into different subtypes (isoforms), which are numbered M1 to M5. The M1 Isoform is found in the brain, for example in the corpus striatum. It is known as the neural type. The M2 Isoform is found on the heart. The M3 mAChR sits on the smooth muscles of blood vessels and glands, such as the salivary glands and pancreas. It is also responsible for the acid production of the parietal cells in the stomach. Either M4, as well as M5 are not yet fully explored, but both occur in the brain.

Nicotinic acetylcholine receptors

The nicotinic acetylcholine receptors (nAChR) are mainly found on the motor end plate. Here they are used to transmit nerve impulses to the muscles. NAChR are known above all in connection with the disease Myasthenia gravis, in which the nicotinic receptors are destroyed by autoantibodies, which ultimately leads to a disruption of muscle excitation.

Alzheimer's disease

Alzheimer's disease, known after its first person describing it, Alois Alzheimer, is a so-called neurodegenerative disease. It occurs particularly in people over the age of 65 and is gradually increasing dementia result. Alzheimer's disease is based on the Destruction of nerve cells due to plaque buildup of beta-amyloid peptides within cells. This cell death is known as Brain atrophy. Acetylcholine-producing neurons are particularly affected, resulting in an ACh deficiency in the brain.

Since numerous cognitive abilities and processes are linked to this messenger substance, behavioral problems and an inability to participate in activities of everyday life increasingly occur in the patient as the disease progresses.

Since a causal therapy is not available to this day, the disease becomes the best possible symptomatic treated. This is mainly done through drug administration Acetylcholinesterase inhibitors like galantamine or rivastigmine, which inhibit the acetylcholine-degrading enzyme. This results in a higher concentration of the neurotransmitter in the brain. The same effect can also be achieved by the administration of Precursor proteins of the ACh reached.

Inactive protein precursors, which are converted into their active form by enzymatic cleavage, are called precursor proteins. Acetylcholine precursor proteins include deanol and meclophenoxate.

Parkinson's disease

The Parkinson's disease (also idiopathic Parkinson's syndrome, IPS for short) is one of the neurodegenerative diseases. The main characteristic of the disease is its main symptoms, which Muscle stiffness (Rigor), Sedentary lifestyle (Bradykinesia) Muscle tremors (tremor) and Postural instability (postural instability) includes (see: Parkinson's disease symptoms). The main cause of this serious disease is the gradual death of nerve cells of the so-called substantia nigra, which is located in the midbrain. Since these nerve cells are mainly responsible for the production of Dopamine are responsible, in the course of the disease there is an increasing lack of dopamine in the brain structure that is essential for movement Basal ganglia. Viewed differently, one can also speak of an excess of the other neurotransmitters. In particular, these are norepinephrine and acetylcholine. In particular, the excess weight of acetylcholine is considered to be the cause of the main symptoms of Parkinson's disease.

The Parkinson's disease therapy mainly includes the gift dopaminergic drugs, a medication that increases the amount of dopamine in the brain. Another therapeutic approach, which is now rarely pursued due to severe side effects, is so-called administration Anticholinergics, also called parasympatholytics. These are substances that suppress the ACh effect by inhibiting the muscarinic acetylcholine receptors. This can compensate for the imbalance in neurotransmitters. Frequently occurring side effects of the anticholinergics concern mainly Limitations in cognitive performance of patients, as well States of confusion, Hallucinations, sleep disorders, as well as minor side effects like Dry mouth.