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Histamine: functions and associated disorders

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Histamine is one of the most important elements in the world of medicine, and its use is common when it comes to treating health problems, especially allergic reactions.

Throughout this article we will see what exactly histamines are, and its effects on the human body.

  • Related article: "The 13 types of allergies, their characteristics and symptoms"

What is histamine?

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

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

History of the discovery of this imidazole amine

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

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From this they began to study its biological effects. But It wasn't until 1927 that histamine was finally found to be found in animals and the human body.. This happened when physiologists Best, Dale, Dudley, and Thorpe succeeded in isolating the molecule from a fresh liver and lung. And this is when it received its name, since 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, that is, This amino acid cannot be generated in the human body and must be obtained through food. The reaction used for its synthesis is decarboxylation, which is catalyzed 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 granules, along with other substances. But they are not the only ones that synthesize it, so do the enterochromaffin cells both in the pylorus region, and the neurons in the hypothalamus.

Mechanism of action

Histamine is a messenger that acts as both 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 receptor is found throughout the body. It is located in the smooth muscle of the bronchi and intestine, where the reception of histamine causes bronchoconstriction and increased bowel movements, respectively. It also increases the production of mucus by the bronchi.

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

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

2. H2 receptor

This type of histamine receptor it is located in a group of specific cells of 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.

TIt is also located in cells of the immune system, such as 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 reduces 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. Thus, as with many other elements of the same type of the organism, it does not fulfill a fixed function, but has several and these depend largely on its location and the context in which 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 the recruitment of cells from the blood, as it is found in the spleen and thymus. Another hypothesis is that it participates 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 that it is exposed to many particles that arrive from outside and can generate a chain reaction in the Body.

Main functions of histamine

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

Despite this, histamine is well known for another less healthy reason, since it is the main implicated in allergic reactions. These are reactions that appear before the invasion of the body itself by certain foreign particles, and you can be born with this characteristic or it can become developed at some specific moment in life, after which it is rare that disappear. Much of the western population suffers from allergies, and one of their main treatments is taking antihistamines.

Now we will go into more detail about some of these functions.

1. Inflammatory answer

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, 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 bind to elements unknown to the body, so-called antigens.

When a mast cell or basophil finds an IgE bound to an antigen, it initiates a response against it, releasing its contents, including histamine. The amine acts on nearby blood vessels, increasing the volume of blood by vasodilation and allowing fluid to escape to the detected area. In addition, it acts as chemotaxis on the other leukocytes, that is, it attracts them to the place. All of this results in inflammation, with its blush, heat, edema and itching, which are nothing more than an unwanted consequence of a process necessary to maintain good health, or at least try.

2. Sleep regulation

Histaminergic neurons, that is, that release histamine, are located in the hypothalamus posterior and tuberomamilar nucleus. From these areas, they extend towards the prefrontal cortex of the brain.

As a neurotransmitter, histamine prolongs wakefulness and reduces sleep, that is, it acts in the opposite way to the melatonin. It is shown that when you are awake, these neurons fire rapidly. In moments of relaxation or fatigue they work to a lesser extent and are deactivated during sleep.

To stimulate wakefulness, histamine makes use of H1 receptors, while to inhibit it it does so through H3 receptors. A) Yes, H1 agonist and H3 antagonist drugs are a good way to treat insomnia. And 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 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 cause 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 which will have to be learned more as the investigations in this line advance.

Major disorders

Histamine is a messenger that is used to activate many tasks, but It 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 hypersensitization, 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 exaggerated, because very little is needed to generate the inflammatory response.

The typical symptoms of this abnormality, such as respiratory problems or a drop in blood pressure, are due to the effects of histamine on H1 receptors. Thus, antihistamines act at the level of this receptor, not allowing histamine to bind to them.

Alimentary 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 found in food due to the absence of the enzyme that carries out this task, DiAmine Oxidase (DAO). This may have been deactivated by genetic or acquired dysfunction, in the same way in which dairy intolerance occurs.

Here symptoms are similar to allergies, and it is believed that they occur due to an excess of histamine in the body. The only difference is that IgE is not present, since mast cells and basophils are not involved. Histamine intolerance can occur more often if you suffer from diseases related to the digestive system.


Histamine is a substance that has effects far beyond its role in 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 pill can make red, itchy skin caused by allergies fade away.

However, it must be borne in mind that as with all pharmacy products, it is advisable not to abuse these histamine pills, and that in certain severe allergy processes, it is necessary to resort to other types of treatments to give them a solution, such as injections; always, yes, in the hands of health personnel duly accredited to practice.

Bibliographic references:

  • Blandina, Patrizio; Munari, Leonardo; Provensi, Gustavo; Passani, Maria B. (2012). "Histamine neurons in the tuberomamillary nucleus: a whole center or distinct subpopulations?". Frontiers in Systems Neuroscience. 6.
  • Marieb, E. (2001). Human anatomy & physiology. San Francisco: Benjamin Cummings. p. 414.
  • Nieto-Alamilla, G; Márquez-Gómez, R; García-Gálvez, AM; Morales-Figueroa, GE; Arias-Montaño, JA (November 2016). "The Histamine H3 Receptor: Structure, Pharmacology, and Function". Molecular Pharmacology. 90 (5): 649–673.
  • Noszal, B.; Kraszni, M.; Racz, A. (2004). "Histamine: fundamentals of biological chemistry". In Falus, A.; Grosman, N.; Darvas, Z. Histamine: Biology and Medical Aspects. Budapest: SpringMed. pp. 15–28.
  • Paiva, T. B.; Tominaga, M.; Paiva, A. C. M. (1970). "Ionization of histamine, N-acetylhistamine, and their iodinated derivatives". Journal of Medicinal Chemistry. 13 (4): 689–692.

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