Generality
Dopamine is an important neurotransmitter of the catecholamine family, with a control function over: movement, so-called working memory, pleasure sensation, reward, prolactin production, sleep regulation mechanisms, some cognitive faculties and the ability to pay attention.
The dopaminergic area includes several brain sites, including the pars compacta of the substantia nigra and the tegmental area of the midbrain.
Abnormal dopamine levels are responsible for several pathological conditions. One of these pathological conditions is the known Parkinson's disease.
What is dopamine?
Dopamine is an organic molecule, belonging to the catecholamine family, which plays the important role of neurotransmitter in the brain of humans and other animals.
Dopamine is also the precursor molecule from which cells, by means of specific processes, derive two other neurotransmitters from the catecholamine family: norepinephrine (or noradrenaline ) and epinephrine (or adrenaline ).
WHAT ARE NEUROTHERABS?
Neurotransmitters are chemicals that allow cells in the nervous system, so-called neurons, to communicate with each other.
In neurons, neurotransmitters reside within small vesicles ; the vesicles are comparable to pockets, delimited by a double layer of phospholipids, completely similar to that of the cytoplasmic membrane of a generic healthy eukaryotic cell.
Inside the vesicles, the neurotransmitters remain inert, so to speak, until, in the neurons in which they reside, a nervous impulse does not occur.
The nerve impulses, in fact, stimulate the release of the vesicles by the neurons that contain them.
With the release of vesicles, neurotransmitters escape from nerve cells, occupy the so-called synaptic space (which is a particular space between two very close neurons) and interact with neighboring neurons, to be precise with the membrane receptors of the aforementioned neurons . The interaction of neurotransmitters with neurons placed in the immediate vicinity transforms the initial nerve impulse into a well-specific cellular response, which depends on the type of neurotransmitter and the type of receptors present on the neurons involved.
In simpler words, neurotransmitters are chemical messengers, which nerve impulses release to induce a certain cellular mechanism.
In addition to dopamine and its derivatives, norepinephrine and epinephrine, other important neurotransmitters of the human being are: glycine, serotonin, melatonin, gamma-aminobutyric acid (GABA) and vasopressin.
CHEMICAL NAME OF DOPAMINE
The chemical name of dopamine is 4- (2-aminoethyl) benzene-1, 2-diol .
HISTORY OF DOPAMINE
Curiously, dopamine is a neurotransmitter that researchers first synthesized in the laboratory and then found in the human brain tissues.
Dated 1910, the merit of the laboratory synthesis of dopamine lies with George Barger and James Ewens, two English chemists of the Wellcome company in London.
To discover, instead, that dopamine is a molecule naturally present inside the brain was the British researcher Kathleen Montagu, in 1957, at the laboratories of Runwell Hospital in London.
One year after the discovery of dopamine in brain tissues, then in 1958, scientists Arvid Carlsson and Nils-Ake Hillarp, employees of the Chemical Pharmacology Laboratories of the National Heart Institute of Sweden, identified and described for the first time the role of neurotransmitter, covered with dopamine.
For this important finding and for having established that dopamine is not only a precursor of norepinephrine and epinephrine, Carlsson also received the Nobel Prize in Physiology or Medicine .
WHERE DOES THE DOPAMINE NAME COME FROM?
The scientific community adopted the term "dopamine", because the precursor molecule, from which George Barger and James Ewens synthesized dopamine, was the so-called L-DOPA.
Chemical structure
As stated, dopamine is a catecholamine.
Catecholamines are organic molecules, in which the presence of a benzene ring combined with two OH hydroxyl groups is recurrent. This benzene ring combined with two OH hydroxyl groups has the chemical formula C 6 H 3 (OH) 2 .
In the case of dopamine, this substance consists in the union between the benzene ring with the two hydroxyl groups, typical of catecholamines, and an ethylamine group .
An ethylamine group is an organic compound with two carbon atoms and one nitrogen, and which has the following chemical formula: CH 2 -CH 2 -NH 2 .
In the light of the two chemical formulas reported above, namely that of the benzene group with the two OH groups and that of the ethylamine group, the final chemical formula of dopamine is: C 6 H 3 (OH) 2 -CH 2 -CH 2 -NH 2 .
The figures below show the chemical structure of a generic catecholamine, a hydroxyl group, an ethylamine group, dopamine and L-DOPA.
CHEMICAL PROPERTIES
Like many molecules made up of an ethylamine group, dopamine is an organic base .
This implies that, in an acidic environment, it is generally in protonated form; while, in a basic environment, it is usually in non-protonated form.
Summary: how and where does it happen?
The natural synthesis pathway (or biosynthesis ) of dopamine includes four basic steps and starts from the amino acid L-phenylalanine .
In a simple and schematic way, the biosynthesis of dopamine can be summarized as follows:
L-phenylalanine ⇒ L-tyrosine ⇒ L-DOPA ⇒ dopamine
The conversion of L-phenylalanine to L-tyrosine and the conversion of L-tyrosine to L-DOPA consist of two hydroxylation reactions. In chemistry, a hydroxylation reaction is a reaction at the end of which a molecule acquires an OH hydroxyl group.
The first hydroxylation reaction, namely L-phenylalanine ⇒ L-tyrosine, takes place thanks to the intervention of an enzyme known as phenylalanine hydroxylase .
The L-tyrosine reaction ⇒ L-DOPA, on the other hand, takes place thanks to the intervention of an enzyme known as tyrosine hydroxylase .
The final step, which from L-DOPA originates dopamine, is a decarboxylation reaction.
In the chemical field, a decarboxylation reaction corresponds to a process at the end of which such a molecule loses one or more COOH carboxyl groups.
To provide the decarboxylation reaction that gives rise to L-DOPA is an enzyme called L-amino acid decarboxylase (or DOPA decarboxylase ).
SUMMARY OF DOPAMINE
In the human body, the biosynthesis of dopamine is mainly due to the so-called neurons of the dopaminergic area and, to a lesser extent, to the medullary portion of the adrenal glands (or adrenal glands ).
Dopaminergic area neurons, or dopaminergic neurons, are nerve cells located in:
- Substantia nigra , precisely in the so-called Pars compacta of the substantia nigra . The substantia nigra (or black substance) takes place in the midbrain, which is one of the three main regions that make up the brainstem.
Despite being part of the brain stem, the black substance acts under the guidance of the nuclei of the base (or basal ganglia ) of the telencephalon; the telencephalon is the brain.
According to various scientific studies, the pars compacta of the substantia nigra is the main site of synthesis of dopamine, present in the human body.
- Ventral tegmental area . Also located at the level of the midbrain, the ventral tegmental area has dopaminergic neurons, whose extensions reach different nerve areas, including: the nucleus accumbens, the prefrontal cortex, the amygdala and the hippocampus.
- Posterior hypothalamus . Prolongations of dopaminergic neurons in the posterior hypothalamus reach the spinal cord.
- Arcuate nucleus of the hypothalamus and paraventricular nucleus of the hypothalamus . The dopaminergic neurons of these two areas have extensions that reach the pituitary. Here, they are responsible for influencing prolactin production.
- Uncertain area of the subthalamus .
DEGRADATION
The natural degradation of dopamine in inactive metabolites can occur in two distinct ways and involves three enzymes:
- monoamine oxidase (or MAO),
- catechol-O-methyltransferase (COMT)
- aldehyde dehydrogenase.
Both modes of natural degradation of dopamine lead to the formation of a substance, known as homovanilic acid (HVA).
Functions
Dopamine performs numerous functions, both in the central nervous system and in the peripheral nervous system .
As for the central nervous system, dopamine is a neurotransmitter that participates in:
- Movement control
- The prolactin hormone secretion mechanism
- The control of memory capacity
- The mechanisms of reward and pleasure
- The control of attention spans
- The control of some aspects of behavior and some cognitive functions
- The mechanism of sleep
- The mood control
- The mechanisms underlying learning
As regards the peripheral nervous system, dopamine acts:
- As a vasodilator
- As a stimulant of sodium excretion, through the urine
- As a factor favoring intestinal motility
- As a factor that reduces lymphocyte activity
- As a factor that reduces insulin secretion by the islets of Langerhans (pancreatic beta cells)
DOPAMINERGIC RECEPTORS
After its release into the synaptic space, dopamine exerts its effects by interacting with the so-called dopaminergic receptors, present on the membrane of different nerve cells.
In mammals - therefore also in humans - there are 5 different subtypes of dopaminergic receptors. The names of these 5 receptor subtypes are very simple: D1, D2, D3, D4 and D5.
The response produced by dopamine depends on the dopaminergic receptor subtype, with which dopamine itself interacts.
In other words, the cellular effects of dopamine vary depending on the dopaminergic receptor involved in the interaction.
In the encephalon, the distribution density of dopaminergic receptors varies from brain area to brain area. Stated another way, each area of the brain has its own amount of dopaminergic receptors.
Biologists believe that this different density of receptor distribution depends on the functions that the brain areas must cover.
DOPAMINE AND MOVEMENT
The motor skills of the human being (correct movements, rapidity of movement, etc.) depend on the dopamine that the substantia nigra releases under the action of the basal ganglia.
In fact, if the dopamine released by the substantia nigra is lower than normal, the movements become slower and uncoordinated. Conversely, if dopamine is quantitatively higher than normal, the human body begins to perform unnecessary movements, very similar to tics.
Thus, the fine regulation of dopamine release by the substantia nigra is essential for the human being to move correctly, performing coordinated gestures and at the right speed.
DOPAMINA AND RELEASE OF PROLACTINE
Dopamine originating in the dopaminergic neurons of the arcuate nucleus and the paraventricular nucleus inhibits the secretion of the hormone prolactin, by the lactotropic cells of the pituitary gland .
As can be easily understood, the absence or reduced presence of dopamine from the aforementioned districts implies a greater activity of the pituitary lactotropic cells, therefore a greater production of prolactin.
Dopamine that inhibits prolactin secretion is called the "prolactin inhibiting factor" (PIF).
To know what the effects of prolactin are, readers can click here.
DOPAMINE AND MEMORY
Several scientific studies have shown that adequate levels of dopamine in the prefrontal cortex improve the so-called working memory .
By definition, working memory is "a system for the temporary maintenance and manipulation of information during the execution of different cognitive tasks, such as understanding, learning and reasoning".
If dopamine levels originating in the prefrontal cortex decrease or increase, working memory begins to suffer.
DOPAMINE, PLEASURE AND REWARD
Dopamine is a mediator of pleasure and reward .
In fact, according to reliable studies, the brain of the human being would release dopamine when it "lives" pleasing circumstances or activities, such as a meal based on good food or satisfactory sexual activity.
The neurons of the dopaminergic area most involved in the reward and pleasure mechanisms are those of the nucleus accumbens and the prefrontal cortex.
DOPAMINE AND ATTENTION
Dopamine originating in the prefrontal cortex is supportive of attention span .
Interesting research has shown that reduced dopamine concentrations in the prefrontal cortex are often associated with a condition known as attention deficit hyperactivity disorder .
DOPAMINE AND COGNITIVE FUNCTIONS
The link between dopamine and cognitive abilities is evident in all morbid conditions characterized by an alteration of the dopaminergic neurons of the prefrontal cortex.
In fact, in the aforementioned morbid conditions, in addition to the already mentioned faculties of attention and working memory, neurocognitive functions, problem-solving skills, etc. may also be affected.
diseases
Dopamine plays a central role in various medical conditions, including: Parkinson's disease, attention deficit hyperactivity disorder (ADHD), schizophrenia / psychosis and addiction to certain drugs and certain drugs .
Moreover, according to some scientific studies, it would be responsible for the painful sensations that characterize some morbid states (fibromyalgia, restless legs syndrome, burning mouth syndrome) and the nausea associated with vomiting .
| Dopamine and addiction | |
Drugs | drugs |
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To know more:
- Parkinson's disease
- ADHD
- Schizophrenia
Curiosity and other information
To complement what has been said so far, here is some additional information on dopamine:
- The conversion of dopamine to noradrenaline is a hydroxylation reaction, which is provided by the enzyme known as dopamine beta-hydroxylase .
Conversion of dopamine to adrenaline, on the other hand, is a reaction that takes place due to the intervention of the enzyme known as phenylethanolamine N-methyltransferase .
- Recent studies have shown that even the ocular retina would host some dopaminergic neurons.
These nerve cells have the particularity of being active during daylight hours and silencing during the hours of darkness.
- The most common dopaminergic receptors in the human nervous system are D1 receptors, followed immediately by D2 receptors.
When compared with the subtypes D1 and D2, the D3, D4 and D5 receptors are present at much lower levels.
- According to experts, the abuse of dopamine of pleasure and reward would also include drug abuse.
Indeed, it seems that taking drugs, such as cocaine, causes an increase in dopamine levels, just like good food or satisfying sexual activity.
- Doctors plan a treatment based on dopamine injections, in the presence of: hypotension, bradycardia, heart failure, heart attack, cardiac arrest and kidney failure.
- Physiological aging, to which every human being is subject, coincides with a decline in dopamine levels in the nervous system.
According to some scientific studies, the decline linked to the advanced age of brain function would be due, in part, to this drop in dopamine levels in the nervous system.
See also: Dopamine Agonist Drugs
