It is during the warmer seasons such as summer and spring that allergies are most prevalent. It is also during these seasons that sales of antihistamines increase. The truth is that these treatments help allergy sufferers to reduce their symptoms, which vary in intensity from person to person, and prevent them from being unable to carry out their daily activities. The histamine present in our body is responsible for regulating multiple biological reactions and plays a major role when we suffer from allergies.
It is not for nothing that the medicines that fight them are called ‘antihistamines’. Here we will see how they work and how they affect histamines in order to counteract some of the effects of allergy in our bodies.
What is histamine?
Histamine is a B-amino-ethyl-imidazole molecule, which is produced from the essential amino acid histidine. The human body is not capable of creating it, so it must be obtained through food..
Su síntesis se realiza mediante una reacción de descarboxilación, catalizada por la enzima L-histidina descarboxilasa.
The main cells responsible for histamine production are mast cells and basophilscomponents of the immune system that store it in their interior along with other substances. This molecule is one of those that have several functions in our body and, therefore, it is responsible for 2 objectives, being a hormone and a neurotransmitter at the same time.
They are not unique to humans; they are also found in other animals and plants. In addition to regulating multiple biological functions, our body uses histamine to send messages to other parts of the body.
It is therefore involved in allergic reactions and other cases of food intoleranceas it is closely linked to the processes of the immune system in general. The history of its discovery and isolation will help us to better understand its presence and functions in the body. In the following, we will explore its historical development:
1910
The molecule was discovered as such in the 1910s by Henry H. Dale and George Barger, British chemists working at the Wellcome Physiological Research Laboratories in London. They were the first to isolate it, working with animal tissues, and eventually identified it as a biologically active amine.
1911
Henry continued histamine research with multiple studies on its physiological effects in animals. He described in detail its effects on smooth muscle contraction, especially in the bronchi and intestine, as well as its ability to dilate blood vessels.
1920-1930
Histamine’s role in allergic and anaphylactic reactions finally uncovered.
Se llega a esa conclusión al observar que pacientes a los que se les inyectaba de forma artificial esta molécula desarrollaban síntomas similares a los que se producían en reacciones de alergia.
Aquella conclusión llevó a una investigación para entender su función en la respuesta inmune.
1940-1950
Once it became clear that histamine is a mediator in allergies and other pathological processes, the first antihistamines were developed..
Estos medicamentos tienen la capacidad de bloquear los receptores de histamina y proporcionar un tratamiento eficaz para los síntomas alérgicos y otras condiciones relacionadas.
1960-1980
During these decades, significant advances were made in the understanding of histamine receptors (H1, H2, H3, and later H4, which we will explain later) and their roles in different tissues and body functions. This made it possible to design more specific and effective drugs.
What are its roles?
Thanks to all the research discussed above and the efforts of scientists, it has been possible to understand that histamine is an indispensable element in the immune system and helps to regulate gastric secretions and intestinal motility in the digestive system.
En el sistema nervioso central también se encarga de and regulate the biological rhythm of sleep, among many other functions.
However, the change of perspective and the crucial discovery came when he observed his involvement in allergic reactions. Allergic reactions occur when the body identifies certain particles as invaders, even though they are not necessarily so. Allergies can be inherited or appear at any time in life, and once they manifest, it is difficult to make them go away. The importance of this finding is that it led to the development of the first antihistamines, as a large proportion of the Western population suffers from some form of allergy with very uncomfortable symptoms.
However, to understand the involvement of histamine in allergies and in our body in general, it is necessary to be more specific and explain its roles separately:
Inflammatory response
One of the main functions of histamine in the immune system is to create inflammation.
Este mecanismo it helps to alert and set in motion a defensive mechanism that helps to isolate and combat problems. This requires mast cells and basophils (which store histamine) to recognise a specific antibody, immunoglobulin E (IgE). These, produced by B-lymphocytes, will bind to foreign elements in the body, called antigens.
When a mast cell or basophil detects immunoglobulin E bound to an antigen, it triggers a response by releasing its contents, including histamine. The task of histamine is to increase blood flow by vasodilation and allow fluid to flow out to the affected area. It also has a chemotactic effect on other leukocytes, attracting them to the site. All these processes are intended to provoke inflammation and warn that something is wrong or there is a problem. The most common visible manifestations are flushing, heat, oedema and itching.
Sleep regulation
Histamine-releasing neurons, known as histaminergic neurons, originate in the posterior hypothalamus and the tuberomammillary nucleus, extending into the prefrontal cortex of the brain. As a neurotransmitter, histamine prolongs wakefulness and reduces sleepthus keeping us awake, as opposed to melatonin, which induces sleep. In fact, when we go to sleep, histamine decreases its activity.
To promote wakefulness, histamine acts on H1 receptors, and if it needs to inhibit wakefulness, it uses H3 receptors. Therefore, drugs that agonise H1 and antagonise H3 are effective in treating insomnia. On the other hand, H1 antagonists and H3 agonists can be used to treat hypersomnia. This is why antihistamines, H1-receptor antagonists, often cause drowsiness, although recent research is leading to the development of allergy-fighting drugs that do not make people sleepy.
Sexual response
During orgasm there is a release of histamine from mast cells in the genital area.
Se ha observado que algunas sexual dysfunctions are related to the lack of this release, such as the inability to reach orgasm. However, an excess of histamine can cause premature ejaculation.
The specific receptor used for this function is currently unknown, but is still under study. It is likely to be a novel receptor, the understanding of which will require further research in this area.
Receivers
Histamine, as mentioned above, is a messenger with the ability to be both a hormone and a neurotransmitter. It all depends on the tissue into which it is released. The receptors present in the tissue determine the function that histamine is to perform. To date, it has been possible to distinguish 4 types of them (it is not excluded that there could be more):
H1 Receiver
This type of receptor is present throughout the body, but especially in the smooth muscle of the bronchi and intestine.
En esa zona la estimulación por la histamina causes bronchial constriction and increased bowel movements.
También aumenta la producción de moco por parte de los bronquios.
However, this is not the only area where they are present. They are widely present in the cells that make up the blood vessels, where they cause vasodilation and increased permeability, as discussed above. In the cells of the immune system, such as leukocytes, they help guide cells to areas where histamine has been released..
In the central nervous system, histamine binds to H1 receptors in different regions, stimulating the release of other neurotransmitters and participating in various processes, such as sleep regulation.
H2 Receiver
Present in a very specific group of cells in the digestive tract (mainly in the parietal cells of the stomach), the function of these receptors is to regulate the production and secretion of gastric acid (HCl). Stimulation of this receptor by histamine triggers the release of acid to facilitate digestion.
In addition to the digestive system, H2 receptors are also found on cells of the immune system (lymphocytes) to promote their response and proliferation..
También están presentes en los mastocitos y basófilos, estimulando la liberación de más sustancias.
H3 Receiver
Together with histamine, H3 generates inhibitory effects, thereby reducing the activity of certain processes..
También afecta al sistema nervioso central, sobre el que disminuye la liberación de diversos neurotransmisores (acetilcolina, serotonina e histamina).
In the stomach, it inhibits the release of gastric acidwhile in the lungs it prevents bronchoconstriction. As with many other elements in the body, its function is varied and depends on its location and the context in which it acts.
H4 Receiver
We come to the last receptor discovered to date, so there is not much information about it available either. Research has indicated that it is found in the spleen and thymus, so a role in blood cell recruitment has been hypothesised. Another hypothesis is that the H4 receptor was involved in allergies and asthma because it is on the membrane of eosinophils and neutrophils, cells of the immune system. It has also been detected in the bronchus, so it is exposed to external particles and could trigger a cascade of reactions in the body. However, further research and laboratory analysis is needed to understand their exact function and role.
On the positive side, histamine is not just limited to triggering inflammatory processes in allergic reactions. In fact, one of its most useful applications is its ability to counteract the effects of allergic reactions. A histamine tablet, given by a health professional, can relieve redness and itching of the skin, 2 of the most common symptoms of allergies.
The fact that a new receptor, H4, has been discovered, reminds us that there is still much to discover and learn. That is why it is so important to have an expert laboratory and a team prepared for any challenge..
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Gracias a ellos unimos fuerzas contigo para desarrollar tecnologías, analizar fármacos y lanzar nuevos tests para ofrecer las últimas innovaciones del mercado.
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