CATECHOLAMINES: SYNTHESIS, RELEASE AND FUNCTIONS - NEUROPSYCHOLOGY - 2024

The catecholamines or aminohormonas are substances containing in their structure a catechol group and a side chain with an amino group. They can function in our body as hormones or as neurotransmitters.

Catecholamines are a class of monoamines that are synthesized from tyrosine. The main ones are dopamine, adrenaline and norepinephrine. They consist of very important neurotransmitters in our body and have multiple functions; they participate in both neural and endocrine mechanisms.

Molecular structure of norepinephrine (noradrenaline), of the catecholamine family.

Some of the central nervous system functions that they control are movement, cognition, emotions, learning, and memory. They also play a fundamental role in responses to stress. In this way, the release of these substances increases when physical or emotional stress is experienced. At the cellular level, these substances modulate neuronal activity by opening or closing ion channels according to the receptors involved.

Catecholamine levels can be seen through blood and urine tests. In fact, catecholamines are bound to approximately 50% of proteins in the blood.

Alterations in catecholamine neurotransmission appear to explain certain neurological and neuropsychiatric disorders. For example, depression is associated with low levels of these substances, unlike anxiety. On the other hand, dopamine seems to play an essential role in diseases such as Parkinson's and schizophrenia.

Biosynthesis of catecholamines

Catecholamines are derived from tyrosine, an amino acid that makes up proteins. It can be derived directly from the diet (as an exogenous source) or synthesized in the liver from phenylalanine (as an endogenous source).

Phenylalanine

Phenylalanine is an essential amino acid for humans. It is obtained through diet, although they are also present in some psychoactive substances.

To have adequate levels of catecholamines, it is important to consume foods rich in phenylalanine, such as red meat, eggs, fish, dairy, chickpeas, lentils, nuts, etc.

Tyrosine

Chemical structure of the amino acid Tyrosine (Source: Clavecin via Wikimedia Commons)

As for tyrosine, it can be found in cheese. For catecholamines to form, tyrosine must be synthesized by a hormone called tyrosine hydroxylase. Once hydroxylated, L-DOPA (L-3,4-dihydroxyphenylalanine) is obtained.

Dopamine and norepinephrine

Then DOPA goes through a decarboxylation process through the enzyme DOPA decarboxylase, producing dopamine.

Dopamine 2D molecule.

From dopamine, and thanks to beta-hydroxylated dopamine, norepinephrine (also called norepinephrine) is obtained.

Norepinephrine molecule

Adrenalin

Epinephrine is made in the medulla of the adrenal glands, which are located above the kidneys. It arises from norepinephrine. Epinephrine arises when norepinephrine is synthesized by the enzyme phenylethanolamine N-methyltransferase (PNMT). This enzyme is only found in cells of the adrenal medulla.

Structure of adrenaline

On the other hand, the inhibition of catecholamine synthesis is produced by the action of AMPT (alpha methyl-p-tyrosine). This is responsible for inhibiting the enzyme tyrosine-hydroxylase.

Where are catecholamines produced?

The main catecholamines originate in the adrenal glands, specifically in the adrenal medulla of these glands. They are produced thanks to cells called chromaffins: in this place adrenaline is secreted in 80%, and noradrenaline in the remaining 20%.

These two substances act as sympathomimetic hormones. That is, they simulate the effects of hyperactivity on the sympathetic nervous system. Thus, when these substances are released into the bloodstream, an increase in blood pressure, greater muscle contraction, and an increase in glucose levels are experienced. As well as acceleration of the heart rate and respiration.

For this reason, catecholamines are essential to prepare for stress, fight or flight responses.

Norepinephrine or norepinephrine

Norepinephrine or norepinephrine is synthesized and stored in postganglionic fibers of peripheral sympathetic nerves. This substance is also produced in cells of the locus coeruleus, in a cell group called A6.

These neurons project to the hippocampus, amygdala, thalamus, and cortex; constituting the dorsal norepinephrineal pathway. This pathway appears to be involved in cognitive functions such as attention and memory.

The ventral pathway, which connects with the hypothalamus, appears to participate in vegetative, neuroendocrine, and autonomic functions.

Dopamine

On the other hand, dopamine can also arise from the adrenal medulla and peripheral sympathetic nerves. However, it works primarily as a neurotransmitter in the central nervous system. In this way, it occurs mainly in two areas of the brain stem: the substantia nigra and the ventral tegmental area.

Specifically, the major groups of dopaminergic cells are found in the ventral region of the midbrain, an area called the "A9 cell group." This zone includes the black substance. They are also located in the A10 cell group (ventral tegmental area).

The A9 neurons project their fibers to the caudate nucleus and to the putamen, forming the nigrostriatal pathway. This is essential for motor control.

While the neurons of the A10 zone pass through the nucleus of accumbens, the amygdala and the prefrontal cortex, forming the mesocorticolimbic pathway. This is essential in motivation, emotions and the formation of memories.

In addition, there is another group of dopaminergic cells in a part of the hypothalamus, which connects with the pituitary gland to exert hormonal functions.

There are also other nuclei in the area of ​​the brain stem that are associated with adrenaline, such as the area postmas and the solitary tract. However, for adrenaline to be released into the blood, the presence of another neurotransmitter, acetylcholine, is necessary.

Release

For the release of catecholamines to occur, the prior release of acetylcholine is necessary. This release can occur, for example, when we detect a hazard. Acetylcholine innervates the adrenal medulla and produces a series of cellular events.

Acetylcholine molecular structure

The result is the secretion of catecholamines into the extracellular space by a process called exocytosis.

How do they act in the body?

There are a series of receptors distributed throughout the body called adrenergic receptors. These receptors are activated by catecholamines, and are responsible for a wide variety of functions.

Usually when dopamine, epinephrine, or norepinephrine bind to these receptors; there is a fight or flight reaction. Thus, the heart rate increases, the muscle tension increases and the pupils dilate. They also influence the gastrointestinal system.

It is important to note that blood catecholamines released by the adrenal medulla exert their effects on peripheral tissues, but not on the brain. This is because the nervous system is separated by the blood-brain barrier.

There are also specific receptors for dopamine, which are of 5 types. These are found in the nervous system, especially in the hippocampus, nucleus accumbens, cerebral cortex, amygdala, and substantia nigra.

Features

Catecholamines can modulate very diverse functions of the body. As mentioned above, they can circulate in the blood or have different effects in the brain (as neurotransmitters).

Next, you will be able to know the functions in which catecholamines participate:

Cardiac functions

Through an increase in adrenaline levels (mainly), there is an increase in the contractile force of the heart. In addition, the frequency of the heartbeat increases. This causes an increase in the supply of oxygen.

Vascular functions

Generally, an increase in catecholamines causes vasoconstriction, that is, a contraction in the blood vessels. The consequence is an increase in blood pressure.

Gastrointestinal functions

Epinephrine appears to reduce motility and gastric and intestinal secretions. As well as contraction of the sphincters. The adrenergic receptors involved in these functions are the a1, a2 and b2.

Urinary functions

Epinephrine relaxes the bladder detrusor muscle (so more urine can be stored). At the same time, it contracts the trigone and the sphincter to allow urinary retention.

However, moderate doses of dopamine increase blood flow to the kidneys, exerting a diuretic effect.

Ocular functions

The increase in catecholamines also causes a dilation of the pupils (mydriasis). In addition to a decrease in intraocular pressure.

Respiratory functions

Catecholamines appear to increase respiratory rate. In addition, it has powerful bronchial relaxing effects. Thus, it reduces bronchial secretions, exerting a bronchodilator action.

Functions in the Central Nervous System

In the nervous system, norepinephrine and dopamine increase alertness, attention, concentration, and stimulus processing.

It makes us react faster to stimuli and make us learn and remember better. They also mediate feelings of pleasure and reward. However, elevated levels of these substances have been associated with anxiety problems.

While low dopamine levels seem to influence the appearance of disturbances in attention, learning difficulties and depression.

Motor functions

Dopamine is the main catecholamine involved in mediating the control of movements. The areas responsible are the substantia nigra and the basal ganglia (especially the caudate nucleus).

In fact, an absence of dopamine in the basal ganglia has been shown to be the origin of Parkinson's disease.

Stress

Catecholamines are very important in regulating stress. The levels of these substances are raised to prepare our body to react to potentially dangerous stimuli. This is how the fight or flight responses appear.

Actions on the immune system

Stress has been shown to influence the immune system, being mediated primarily by adrenaline and norepinephrine. When we are exposed to stress, the adrenal gland releases adrenaline, while the nervous system secretes norepinephrine. This innervates the organs involved in the immune system.

A very prolonged increase in catecholamines produces chronic stress and a weakening of the immune system.

Analysis of catecholamines in urine and blood

The body breaks down catecholamines and excretes them in the urine. Therefore, through a urine analysis, the amount of catecholamines secreted in a 24-hour period can be observed. This test can also be done through a blood test.

This test is usually done to diagnose tumors in the adrenal glands (pheochromocytoma). A tumor in this area would cause too many catecholamines to be released. What would be reflected in symptoms such as hypertension, excessive sweating, headaches, tachycardia and tremors.

High levels of catecholamines in the urine can also manifest any type of excessive stress, such as infections throughout the body, surgeries or traumatic injuries.

Although these levels can be altered if they have taken medications for blood pressure, antidepressants, drugs or caffeine. In addition, being cold can increase the levels of catecholamines in the analysis.

However, low values ​​may indicate diabetes or alterations in the activity of the nervous system.

References

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