The Noradrenaline (NA) or norepinephrine (NE), is a chemical that our body creates naturally and can act as a hormone and neurotransmitter.
Together with Dopamine and the adrenalin , Belongs to the family of the Catecholamines ; Substances that are usually associated with physical or emotional stress.
Noradrenaline has multiple functions. As a stress hormone, it seems to affect areas of the brain where attention and reaction to stimuli are controlled. Accompanied by the adrenaline, it is responsible for the fight or flight response by directly increasing the heart rate.
It has traditionally been related to motivation, alertness and wakefulness, level of consciousness, sleep regulation, appetite, sexual and aggressive behavior... As well as monitoring mechanisms learning , memory And reward. However, these functions are usually performed with the help of some other neurotransmitter such as dopamine or Serotonin (Téllez Vargas, 2000).
On the other hand, a decrease in noradrenaline appears to cause low blood pressure, bradycardia (low heart rate), decrease in body temperature and depression .
Noradrenaline exerts its effects when it binds to so-called"adrenergic receptors"or"noradrenergic receptors". Thus, the parts of the organism that produce norepinephrine or where it acts are called noradrenergic.
In addition to being produced in our body, noradrenaline can be injected for therapeutic purposes in people who have extreme hypotension. There are also drugs that alter the natural levels of this substance, such as cocaine and amphetamines.
The term"noradrenaline"comes from the Latin, and means"in or next to the kidneys". Its synonym"norepinephrine"is derived from the chemical prefix"nor-", which indicates that it is the next homologue of epinephrine (adrenaline). This is because the chemical structures of noradrenaline and adrenaline are very similar, varying only one atom.
Differences between norepinephrine and adrenaline
The adrenalin Is a hormone produced by the adrenal medulla, which is the nucleus of the adrenal glands. These are located just above the kidneys (hence the term). This substance also acts as a neurotransmitter in our brain, but it is not as important as noradrenaline.
As to its structure, adrenaline or epinephrine contains a methyl group attached to its nitrogen. On the other hand, in norepinephrine, instead of a methyl group it has a hydrogen atom.
How is norepinephrine synthesized?
Norepinephrine is created in the sympathetic nervous system from an amino acid called Tyrosine , Which can be purchased directly from the diet in foods such as cheese.
However, it can also be derived from the Phenylalanine . This last one is one of the essential amino acids for the human being and also is captured through the feeding. Specifically, it is found in foods rich in proteins such as red meats, eggs, fish, milk, asparagus, chickpeas, peanuts, etc.
Tyrosine is catalyzed by the enzyme Tyrosine-Hydroxylase (TH), which converts it into levodopa (L-DOPA). In contrast, the compound AMPT (Alpha-Methyl-p-tyrosine) is an enzyme that has the opposite effect. That is, it inhibits the conversion of tyrosine to L-DOPA; Thus blocking the production of both dopamine and noradrenaline.
Then L-DOPA is transformed into dopamine thanks to the activity of the enzyme DOPA decarboxylase.
As described by Carlson (2006), many neurotransmitters are synthesized in the cytoplasm Of the cells of our brain. Later they are stored in a kind of tiny bags called" Synaptic vesicles ". However, for the synthesis of noradrenaline the last step occurs inside these vesicles.
Originally, the vesicles are filled with dopamine. Within the vesicles there is an enzyme called dopamine-β-hydroxylase, which is responsible for converting dopamine into noradrenaline.
In these vesicles there is also the fusaric acid compound, which inhibits the activity of the enzyme dopamine-β-hydroxylase to control noradrenaline production, and does not affect the amount of dopamine required.
How does norepinephrine degrade?
When there is excess noradrenaline in the terminal bud of neurons, it is destroyed by monoamine oxidase type A (MAO-A). It is an enzyme that converts noradrenaline into an inactive substance (this resulting substance is called a metabolite).
The goal is that norepinephrine does not continue to effect the body, since having high levels of this neurotransmitter could have dangerous consequences.
It can also be degraded by the enzyme catechol-O-methyl transfer (COMT), or converted into adrenaline by an enzyme in the adrenal medulla called PNMT (Phenylethanolamine N-methyltransferase).
The major metabolites that arise after this degradation are VMA (vanilylmandelic acid) in the periphery, and MHPG (3-Methoxy-4-hydroxyphenylglycol) in the central nervous system. Both are excreted in the urine, so they can be detected in a test.
Noradrenergic system and brain parts involved
Noradrenergic neurons are reduced in our brain And are organized in small nuclei. The most important nucleus is the locus coeruleus that is located in the dorsal protuberance. Although they also exist in the medulla bulb and thalamus. However, they project into many other areas of the brain and their effects are very powerful. Virtually all regions of the brain receive afferentations from noradrenergic neurons.
The axons of these neurons act on the adrenergic receptors of various parts of the nervous system, such as: cerebellum , spinal cord , Thalamus, Hypothalamus , Basal ganglia, hippocampus , amygdala , Septum, neocortex (Carlson, 2006). In addition to the cingulate gyrus and striatum.
The main effect of the activation of these neurons is the increase in the surveillance capacity. That is, an increase in attention to detect events in the environment.
In 1964 Dahlström and Fuxe defined several important cell nuclei. They called them"A", which comes from"aminérgico". Fourteen"zones A"were described: the first seven contain the neurotransmitter noradrenaline, while the following contain dopamine.
The noradrenergic A1 group is located near the lateral reticular nucleus and is critical for controlling body fluid metabolism. On the other hand, group A2, is in a part of the trunk-cephalon called solitary nucleus. These cells participate in stress responses and control of appetite and thirst. Groups 4 and 5 project primarily to the spinal cord.
However, the locus coeruleus is the most important area; And contains the group A6. A high activity of the nucleus coeruleus is associated with monitoring and reaction rate. In contrast, a drug that suppresses activity in this area produces a strong sedative effect.
On the other hand, outside the brain, noradrenaline functions as a neurotransmitter in the sympathetic ganglia located near the abdomen or spinal cord. It is also released directly into the blood from Kidney glands, Structures above the kidneys that regulate stress responses.
Noradrenergic receptors
There are different types of noradrenergic receptors, which are distinguished according to their sensitivity to certain compounds. These receptors are also called adrenergic, because they usually catch both adrenaline and noradrenaline.
In the central nervous system, neurons contain adrenergic receptors β1 and β2, and α1 and α2. These four types of receptors are also found in several organs other than the Encephalon . A fifth type called the β3 receptor is found outside the central nervous system, mainly in adipose tissue (fat).
All these receptors have both excitatory and inhibitory effects. For example, the α 2 receptor generally has a net effect of decreased noradrenaline released (inhibitory). While the rest of receptors normally produce observable excitatory effects.
What functions are associated with noradrenaline?
Norepinephrine is related to a wide variety of functions. But above all it is linked to a state of physical and mental activation, which prepares us to react to the events of our environment. That is, it sets in motion the responses of struggle or flight.
Thus, it allows the body to respond adequately to situations of stress Through increased heart rate, increased blood pressure, dilated pupils, and widening of the airways.
In addition, it causes narrowing of blood vessels in non-essential organs. That is, it reduces blood flow to the gastrointestinal system; Blocking gastrointestinal motility. Just as it inhibits emptying of the bladder. This happens because our body sets priorities, and assumes that it is more important to devote energy to the defense of a danger than to the excretion of waste.
It is possible to further detail the effects of this substance according to the part of the nervous system in which it acts.
In the Sympathetic Nervous System
It is the main neurotransmitter of Sympathetic nervous system , And consists of a series of ganglia. The ganglia of the sympathetic chain are located next to the spinal cord, in the chest and in the abdomen. These establish connections with a wide variety of organs such as the eyes, salivary glands, heart, lungs, stomach, kidneys, bladder, reproductive organs... As well as the adrenal glands.
The goal of noradrenaline is to modify the activity of organs to maximize a rapid reaction of the body to certain events. The sympathetic effects would be:
- Increase in the amount of blood pumped by the heart.
- It acts on the arteries, causing increase of the blood pressure through the constriction of the blood vessels.
- Quickly burn calories in adipose tissue to generate body heat. It also promotes lipolysis, a process that transforms fat into energy sources for muscles and other tissues.
- Increase in eye moisture and dilation of the pupils.
- Complex effects on the immune system (some processes appear to be activated while others are deactivated).
- Increased glucose production through its performance in the liver. Remember that glucose is the body's main energy source.
- In the pancreas, noradrenaline promotes the release of a hormone called glucagon. This potentiates the production of glucose by the liver.
- It facilitates the skeletal muscles to capture the glucose necessary to act.
- In the kidneys, it releases renin and retains sodium in the blood.
- Reduces the activity of the gastrointestinal system. In particular, it decreases blood flow to that area, and inhibits gastrointestinal mobility, as well as the release of digestive substances.
These effects can be counteracted in the Parasympathetic nervous system With a substance called Acetylcholine . It has the opposite functions: it reduces the heart rate, it facilitates a state of relaxation, it increases the intestinal motility promoting the digestion, it favors the micción, contraction of the pupils, etc.
In the Central Nervous System
Noradrenergic neurons in the brain primarily promote a state of alert arousal and preparation for action. The main structure responsible for the"mobilization"of our central nervous system is the locus coeruleus, which participates in the following effects:
- Increases vigilance, a state in which we are more attentive to our environment and ready to respond to any event.
- Increased attention and concentration.
- Improves the processing of sensory stimuli.
- As a consequence, greater release of noradrenaline promotes memory. Specifically, it increases the ability to store memories and learn; As well as recover data already stored. It also improves work memory .
- It reduces the reaction times, that is, it takes much less to process the stimuli and to issue a response.
- Increased anxiety and anxiety .
During sleep less noradrenaline is released. Levels are stable during wakefulness, and they elevate much more in unpleasant, stressful, or dangerous situations.
For example, pain, bladder distention, heat, cold, or difficulty breathing produce increases in noradrenaline. Although states of fear or intense pain are linked to very high levels of activity of the locus coeruleus, and, therefore, more noradrenaline.
Therapeutic use of noradrenaline
There is a great variety of drugs whose effects affect noradrenergic systems throughout our body. They are mainly used for cardiovascular problems and certain psychiatric conditions.
There are sympathomimetic drugs, or also called adrenergic agonists, that mimic or potentiate some of the effects of existing noradrenaline. In contrast, sympatholytic drugs (or adrenergic antagonists) have the opposite effect.
Noradrenaline itself would be Sympathomimetic , And can be administered directly by intravenous injection in cases of Hypotension serious.
On the other hand, norepinephrine-inhibiting drugs may focus on blocking beta receptors. They are used to treat high blood pressure, cardiac arrhythmia or heart failure, glaucoma, angina pectoris or Marfan syndrome .
However, its use is increasingly limited as it has serious side effects, mainly for diabetics.
There are also drugs that block alpha receptors, which have a wide variety of uses because their effects are somewhat more complex. They can be used to relax the muscles of the bladder in certain conditions like the expulsion of stones in the bladder.
In particular, alpha 1 receptor inhibitors are also useful for disorders such as generalized anxiety, panic disorder, and post-traumatic stress disorder.
While those blocking alpha 2 receptors, they have a final effect of norepinephrine potentiation. They have been widely used to treat depression, since it has traditionally been thought that these patients have low levels of noradrenaline.
Drugs that increase noradrenaline levels have also been used in patients with Attention Deficit Disorder and Hyperactivity. Mainly methylphenidate, which also increases the amount of dopamine.
References
- Carlson, N.R. (2006). Physiology of behavior 8ª Ed. Madrid: Pearson. Pp: 129-130.
- Cox, S. (s.f.). Norepinephrine . Retrieved on November 23, 2016, from RICE University.
- Dahlstroem A, Fuxe K (1964). "Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiologica Scandinavica. Supplementum. 232 (Supplement 232): 1-55.
- Noradrenaline (Norepinephrine). (April 23, 2014). Obtained from Netdoctor.
- Norepinephrine . (S.f.). Retrieved on November 23, 2016, from Wikipedia.
- Prokopova, I. (2009). [Noradrenaline and behavior]. Ceskoslovenska fysiologie / Ustredni ustav biologicky, 59 (2), 51-58.
- Téllez Vargas, J. (2000). Noradrenaline. His role in depression. Revista Colombiana de Psiquiatría, 1: 59-73.