Histamine is a molecule that acts in our body both as a hormone and a neurotransmitter, to regulate different biological functions.

It is present in significant quantities in both plants and animals, and is used by cells as a messenger . In addition, it plays a very important role in allergies, food intolerance and the processes of the immune system in general. Let’s see what its secrets and most important characteristics are.

History of its discovery

Histamine was first discovered in 1907 by Windaus and Vogt, in an experiment where they synthesized it from imidazole propionic acid, although they were unaware that it existed naturally until 1910, when they saw it being manufactured by the ergot fungus.

From there they began to study its biological effects. But it was not until 1927 that it was finally discovered that histamine is found in animals and the human body . This happened when physiologists Best, Dale, Dudley and Thorpe managed to isolate the molecule from a fresh liver and lung. And this is when it received its name, as it is an amine that is significantly found in tissues (histo).

Synthesis of histamine

Histamine is a B-amino-ethyl-imidazole, a molecule that is manufactured from the essential amino acid histidine, i.e. this amino acid cannot be generated in the human body and must be obtained through food . The reaction used for its synthesis is a decarboxylation, which is catalysed by the enzyme L-histidine decarboxylase.

The main cells that carry out the manufacture of histamine are mast cells and basophils , two components of the immune system that store it inside of granules, along with other substances. But they are not the only ones that synthesize it, so do the enterochromaffin cells in both the pylorus region and the neurons in the hypothalamus area.

Mechanism of action

Histamine is a messenger that acts both as a hormone and a neurotransmitter, depending on which tissue it is released into. As such, the functions it activates will also be carried out thanks to the action of histamine receptors . Of the latter, there are up to four different types, although there may be more.

1. H1 receiver

This type of receiver is distributed throughout the body. It is located in the smooth muscle of the bronchi and the intestine , where the reception of histamine causes a bronchoconstriction and an increase in intestinal movements, respectively. It also increases the production of mucus by the bronchi.

Another location for this receptor is in the cells that form the blood vessels, where it causes vasodilation and increased permeability. Leukocytes (i.e. cells of the immune system) also have H1 receptors on their surface, which serve to target the area where histamine has been released.

In the Central Nervous System (CNS), histamine is also captured in different areas by the H1, and this stimulates the release of other neurotransmitters and acts on different processes, such as sleep regulation.

2. H2 receiver

This type of histamine receptor is located on a group of specific cells in the digestive tract, specifically the parietal cells of the stomach . Its main function is the production and secretion of gastric acid (HCl). Reception of the hormone stimulates the release of acid for digestion.

T is also located in cells of the immune system, such as in the lymphocytes , favoring their response and proliferation; or in the mast cells and basophils themselves, stimulating the release of more substances.

3. H3 receiver

This is a receptor with negative effects, that is, it inhibits processes when receiving histamine . In the CNS, it decreases the release of different neurotransmitters, such as acetylcholine, serotonin or histamine itself. In the stomach it inhibits the release of gastric acid, and in the lung it prevents bronchoconstriction. Therefore, as with many other elements of the same type in the body, it does not have a fixed function, but rather several, and these depend largely on its location and the context in which it works.

4. H4 receiver

It is the last histamine receptor discovered, and it is not yet known which processes it activates . There are indications that it presumably acts on blood cell recruitment, since it is found in the spleen and thymus. Another hypothesis is that it is involved in allergies and asthma, since it is located in the membrane of eosinophils and neutrophils, cells of the immune system, as well as in the bronchus, so it is exposed to many particles that come from outside and can generate a chain reaction in the body.

Main functions of histamine

Among its functions of action we find that it is essential to favour the response of the immune system and that it works at the level of the digestive system regulating gastric secretions and the motility of the intestine. It also acts on the central nervous system by regulating the biological rhythm of sleep , among many other tasks in which it participates as a mediator.

Despite this, histamine is well known for another, less healthy reason, as is the main one involved in allergic reactions . These are reactions that appear before the invasion of the body itself by certain foreign particles, and can be born with this characteristic or can be developed at some specific time in life, from which it rarely disappears.A large part of the Western population suffers from allergies, and one of their main treatments is to be medicated with antihistamines.

We will now go into more detail about some of these functions.

Inflammatory response

One of the main known functions of histamine occurs at the level of the immune system with the generation of inflammation, a defensive action that helps isolate the problem and fight it . In order to initiate it, mast cells and basophils, which store histamine inside them, need to recognize an antibody, specifically Immunoglobulin E (IgE). Antibodies are molecules produced by other cells of the immune system (B-lymphocytes), and are capable of binding to elements unknown to the body, the so-called antigens .

When a mast cell or basophil encounters an IgE bound to an antigen, it initiates a response to the antigen, releasing its contents, histamine being among these. The amine acts on the nearby blood vessels, increasing the blood volume by vasodilation and allowing the exit of liquid to the detected area. In addition, it acts as chemotaxis on the other leukocytes, that is, it attracts them to the site. All this translates into an inflammation , with its blushing, heat, edema and itching, which are nothing more than an undesired consequence of a process necessary to maintain a good state of health, or at least try to do so.

2. Sleep regulation

Histaminergic neurons, i.e. those that release histamine, are located in the posterior hypothalamus and tuberomamilary nucleus. From these areas, they extend to the prefrontal cortex of the brain.

As a neurotransmitter, histamine prolongs wakefulness and reduces sleep , i.e. it acts in the opposite way to melatonin. It has been shown that when you are awake, these neurons are quickly activated. In moments of relaxation or tiredness they work less and are deactivated during sleep.

To stimulate wakefulness, histamine makes use of H1 receptors, while to inhibit it it makes use of H3 receptors. Thus, H1 agonist and H3 antagonist drugs are a good means of treating insomnia . Conversely, H1-antagonists and H3-agonists can be used to treat hypersomnia. This is why antihistamines, which are H1-receptor antagonists, have drowsy effects.

3. Sexual response

It has been seen that during orgasm there is a release of histamine in the mast cells located in the genital area . Some sexual dysfunctions are associated with the lack of this release, such as the absence of orgasm in the relationship. Therefore, excess histamine can lead to premature ejaculation.

The truth is that the receptor used to carry out this function is currently unknown and is a reason for study; it is probably a new one and one that will have to be known more as research in this line advances.

Major disorders

Histamine is a messenger that is used to activate many tasks, but is also involved in abnormalities that affect our health .

Allergy and histamines

One of the main disorders and most commonly associated with histamine release is type 1 hypersensitisation, a phenomenon better known as allergy .

Allergy is an exaggerated response to a foreign agent, called an allergen , which in a normal situation should not cause this reaction. It is said to be exaggerated, because very little is needed to generate the inflammatory response.

Typical symptoms of this abnormality, such as breathing problems or a drop in blood pressure, are due to the effects of histamine on H1-receptors. Therefore, anti-histamines act at the level of this receptor, not allowing histamine binding to them .

Food intolerance

Another anomaly associated with histamine is food intolerance. In this case, the problem occurs because the digestive system is unable to degrade the messenger it finds in food due to the absence of the enzyme that performs this task, DiAmine Oxidase (DAO). This may have been deactivated by a genetic dysfunction or acquired, in the same way that dairy intolerance occurs.

Here the symptoms are similar to those of an allergy , and are believed to occur because there is an excess of histamine in the body. The only difference is that there is no IgE present, as neither mast cells nor basophils are involved. Histamine intolerance may occur more frequently if you suffer from diseases related to the digestive system.

Conclusions

Histamine is a substance that has effects far beyond its role in the inflammatory processes linked to allergies. However, in practice, one of its most interesting and useful applications is its ability to mitigate allergy events; for example, a relatively small histamine tablet can cause the redness and itchiness of the skin to fade in an allergy.

Referencias bibliográficas:

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