Where is histamine produced in the human body? The phenomenon of histamine intolerance. Difficult but important

This compound was first obtained synthetically in 1907, and only later, after establishing the fact of its association with animal tissues and the mast cells present in them, did it get its name and scientists understood what it was. histamine and what are histamine receptors . Already in 1910, the English physiologist and pharmacologist Henry Dale (winner Nobel Prize 1936 for his work on the role of acetylcholine in the transmission of nerve impulses) proved that histamine is a hormone and demonstrated bronchospastic and vasodilating properties when administered intravenously to animals. Further studies focused mainly on the similarity of the processes that develop in response to the introduction of an antigen to a sensitized animal and the biological effects that occur after hormone injections. Only in the 50s of the last century it was established that histamine is contained in and released from them during allergies.

Histamine metabolism (synthesis and breakdown)

From the foregoing, it is clear what histamine is, but how it is synthesized and further metabolized.

Basophils and mast cells are the main formations of the body in which histamine is produced. The mediator is synthesized in the Golgi apparatus from the amino acid histidine by the action of histidine decarboxylase (see the synthesis scheme above). The newly formed amine is complexed with heparin or structurally related proteoglycans by ionic interaction with the acidic residues of their side chains.

Histamine secreted after synthesis is rapidly metabolized (half-life - 1 min) mainly in two ways:

1. oxidation (30%),
2. methylation (70%).

Most of the methylated product is excreted through the kidneys, and its concentration in the urine can be a criterion for the total endogenous secretion of histamine. Small amounts of the mediator are spontaneously secreted by resting mast cells of the skin at a level of approximately 5 nmol, which exceeds the concentration of the hormone in blood plasma (0.5-2.0 nmol). Except mast cells and basophils, histamine can be produced by platelets, cells of the nervous system and stomach.

Histamine receptors (H1, H2, H3, H4)

The range of biological effects of histamine is quite wide, due to the presence of at least four types of histamine receptors:

• H 1,
• H 2
• H 4 .

They belong to the most common class of sensors in the body, which includes visual, olfactory, chemotactic, hormonal, neurotransmission, and a number of other receptors. The diversity of structures within a class in vertebrates can range from 1000 to 2000, and total corresponding genes usually exceeds 1% of the genome volume. These are folded protein molecules that "flash" the outer cell membrane 7-fold and are associated with G-protein from its inner side. G-proteins are also represented by a large family. They are united by a common structure (they consist of three subunits: α, β and γ) and the ability to bind the nucleotide guanine (hence the name "guanine-binding proteins" or "G-proteins").

There are 20 known variants of chains Gα, 6 - Gβ and 11 - Gγ. During signal transduction (see figure above), the resting-linked G-protein subunits break down into an α monomer and a βγ dimer. Based on the difference in the structure of the α-subunits, G-proteins are divided into 4 groups (α s , α i , α q , α 12). Each group has its own characteristics of the initiation of intracellular signaling pathways. Thus, in a particular case of ligand-receptor interaction, the response of the cell is determined both by the specificity and structure of the histamine receptor itself and by the properties of the G-protein associated with it.

The noted features are also characteristic of histamine receptors. They are encoded by individual genes located on different chromosomes and are associated with different G-proteins (see table below). In addition, there are significant differences in the tissue localization of individual types of H-receptors. With allergies, most of the effects are realized through H 1 -histamine receptors. The observed activation of the G-protein and the release of the α q / 11 chain initiate through phospholipase C the cleavage of membrane phospholipids, the formation of inositol triphosphate, the stimulation of protein kinase C and the mobilization of calcium, which is accompanied by the manifestation of cellular reactivity, sometimes called "allergy to histamine" (for example, in the nose - rhinorrhea, in the lungs - bronchospasm, in the skin - redness, urticaria and blistering). Another signaling pathway coming from the H 1 -histamine receptor can induce the activation of the transcription factor NF-κB, which is usually realized in the formation of an inflammatory response.

Histamine is able to enhance the Th2 immune response by suppressing the production of IL-12 and activating the synthesis of IL-10 in antigen-presenting cells. In addition, it increases the expression of CD86 on the surface of these cells.

However, the effects of histamine at the level of T-lymphocytes may be different (up to the opposite). So the mediator through histamine H 1 receptors enhances the proliferation of stimulated Th1 cells and the production of IFN-γ. At the same time, it can have an inhibitory effect on the mitotic activity of Th2-lymphocytes and the synthesis of IL-4 and IL-13 by these cells. In this case, the effects are realized through H 2 -histamine receptors. The latter phenomena seem to reflect a feedback mechanism aimed at attenuating the allergic reaction. Under the action of IL-3, which is a growth factor for mastocytes and basophils, and also an inducer of histidine decarboxylase, there is an increase in the expression of H1-histamine receptors on Th1 (but not Th2) lymphocytes.

K.V. Shmagel and V.A. Chereshnev

Histamine is organic, i.e. originating from living organisms, a compound that has amine groups in its structure, i.e. biogenic amine. Histamine performs many important functions in the body, more on that later. Excess histamine leads to various pathological reactions. Where does excess histamine come from and how to deal with it?

Sources of histamine

• Histamine is synthesized in the body from the amino acid histidine: This histamine is called endogenous.
• Histamine can be ingested through food. In this case, it is called exogenous
• Histamine is synthesized by the intestinal microflora and can be absorbed into the blood from digestive tract. With dysbacteriosis, bacteria can produce an excessively large amount of histamine, which causes pseudo-allergic reactions.

It has been established that endogenous histamine is much more active than exogenous.

Synthesis of histamine

In the body, under the influence of histidine decarboxylase with the participation of vitamin B-6 (pyridoxal phosphate), the carboxyl tail is split off from histidine, so the amino acid is converted into an amine.

Synthesis takes place:

1. In the gastrointestinal tract in the cells of the glandular epithelium, where histidine, which comes with food, is converted into histamine.
2. In mast cells (labrocytes) connective tissue, as well as other organs. There are especially many mast cells in places of potential damage: mucous membranes respiratory tract(nose, trachea, bronchi), epithelium lining blood vessels. Histamine synthesis is accelerated in the liver and spleen.
3. In white blood cells - basophils and eosinophils

The histamine produced is either stored in mast cell granules or white blood cells or rapidly degraded by enzymes. If the balance is disturbed, when histamine does not have time to break down, free histamine behaves like a bandit, wreaking havoc in the body, called pseudo-allergic reactions.

The mechanism of action of histamine

Histamine acts by binding to specific histamine receptors, which are designated H1, H2, H3, H4. The amine head of histamine interacts with aspartic acid, which is inside cell membrane receptor, and triggers a cascade of intracellular reactions that manifest themselves in certain biological effects.

Histamine receptors

• H1 receptors are located on the surface of the membranes of nerve cells, smooth muscle cells of the respiratory tract and blood vessels, epithelial and endothelial cells (skin cells and lining of blood vessels), white blood cells responsible for neutralizing foreign agents

Their activation by histamine causes external manifestations of allergy and bronchial asthma: spasm of the bronchi with difficulty breathing, spasm of the smooth muscles of the intestine with pain and profuse diarrhea, increased vascular permeability, resulting in edema. Increased production of inflammatory mediators - prostaglandins, which damage the skin, which leads to skin rashes(urticaria) with redness, itching, rejection of the surface layer of the skin.

Receptors located in nerve cells are responsible for the overall activation of brain cells, histamine turns on the wakefulness mode.

Drugs that block the action of histamine on H1 receptors are used in medicine to inhibit allergic reactions. These are diphenhydramine, diazolin, suprastin. Since they block receptors found in the brain along with other H1 receptors, side effect of these remedies is the feeling of drowsiness.

• H2 receptors are found in the membranes of the parental cells of the stomach - those cells that produce hydrochloric acid. Activation of these receptors leads to an increase in acidity gastric juice. These receptors are involved in the processes of food digestion.

Exist pharmacological preparations selectively block histamine H2 receptors. These are cimetidine, famotidine, roxatidine, etc. They are used in the treatment peptic ulcer stomach, because they suppress the production of hydrochloric acid.

In addition to affecting the secretion of the gastric glands, H2 receptors trigger secretion in the respiratory tract, which provokes allergy symptoms such as a runny nose and sputum in the bronchi in bronchial asthma.

In addition, stimulation of H2 receptors affects the immune response:

IgE is inhibited - immune proteins that pick up a foreign protein on the mucous membranes, inhibits the migration of eosinophils (immune white blood cells responsible for allergic reactions) to the site of inflammation, enhances the inhibitory effect of T-lymphocytes.

• H3 receptors are located in nerve cells, where they take part in the conduction of a nerve impulse, and also trigger the release of other neurotransmitters: norepinephrine, dopamine, serotonin, acetylcholine. Some antihistamines, such as diphenhydramine, along with H1 receptors, act on H3 receptors, which manifests itself in a general inhibition of the central nervous system, which is expressed in drowsiness, inhibition of reactions to external stimuli. Therefore, non-selective antihistamines should be taken with caution by persons whose activities require rapid reactions, such as drivers Vehicle. Currently, selective drugs have been developed that do not affect the functioning of H3 receptors, these are astemizole, loratadine, etc.
• H4 receptors are found in white blood cells - eosinophils and basophils. Their activation triggers immune responses.

The biological role of histamine

Histamine is related to 23 physiological functions, because it is a highly active chemical substance that easily enters into interaction reactions.

The main functions of histamine are:

• Regulation of local blood supply
• Histamine is an inflammatory mediator.
• Regulation of gastric acidity
• Nervous regulation
• Other features

Regulation of local blood supply

Histamine regulates the local blood supply to organs and tissues. With increased work, for example, muscles, a state of lack of oxygen occurs. In response to local tissue hypoxia, histamine is released, which causes the capillaries to expand, blood flow increases, and with it, the flow of oxygen also increases.

Histamine and Allergy

Histamine is the main mediator of inflammation. This function is associated with its participation in allergic reactions.

It is contained in bound form in the granules of mast cells of the connective tissue and basophils and eosinophils - white blood cells. An allergic reaction is an immune response to an invading foreign protein called an antigen. If this protein has already entered the body, immunological memory cells retained information about it and transferred it to special proteins - immunoglobulins E (IgE), which are called antibodies. Antibodies have the property of specificity: they recognize and react only to their own antigens.

When a protein-antigen enters the body again, they are recognized by antibodies-immunoglobulins, which were previously sensitized by this protein. Immunoglobulins - antibodies bind to an antigen protein, forming an immunological complex, and this whole complex is attached to the membranes of mast cells and / or basophils. Mast cells and/or basophils respond to this by releasing histamine from the granules into the extracellular environment. Together with histamine, other inflammatory mediators leave the cell: leukotrienes and prostaglandins. All together they give a picture allergic inflammation, which manifests itself in different ways, depending on the primary sensitization.

• From the skin: itching, redness, swelling (H1 receptors)
• Respiratory tract: smooth muscle contraction (H1 and H2 receptors), mucosal edema (H1 receptors), increased mucus production (H1 and H2 receptors), decreased lumen of blood vessels in the lungs (H2 receptors). This is manifested in a feeling of suffocation, lack of oxygen, cough, runny nose.
• Gastrointestinal tract: contraction of the smooth muscles of the intestine (H2 receptors), which manifests itself in spastic pain, diarrhea.
• Cardiovascular system: drop in blood pressure (H1 receptors), impaired heart rate(H2 receptors).

The release of histamine from mast cells can be carried out by an exocytic method without damage to the cell itself, or a rupture of the cell membrane occurs, which leads to a simultaneous entry into the blood a large number both histamine and other inflammatory mediators. As a result, such a formidable reaction occurs as anaphylactic shock with a drop in pressure below critical, convulsions, and disruption of the heart. The condition is life-threatening and even urgent medical assistance does not always save.

At elevated concentrations, histamine is released in all inflammatory responses, both immune-related and non-immune.

Regulation of gastric acidity

Enterochromaffin cells of the stomach release histamine, which through H2 receptors stimulates parietal (pariental) cells. Parietal cells begin to absorb water and carbon dioxide from the blood, which are converted into carbonic acid by the enzyme carbonic anhydrase. Inside the parietal cells, carbonic acid breaks down into hydrogen ions and bicarbonate ions. Bicarbonate ions are sent back to the bloodstream, and hydrogen ions enter the stomach lumen through the K + \ H + pump, lowering the pH to the acid side. The transport of hydrogen ions comes with the expenditure of energy released from ATP. When the pH of the gastric juice becomes acidic, the release of histamine stops.

Regulation of the nervous system

In the central nervous system, histamine is released into synapses, the junctions between nerve cells. Histamine neurons are found in the posterior lobe of the hypothalamus in the tuberomammylar nucleus. The processes of these cells diverge throughout the brain, through the medial bundle forebrain they go to the cerebral cortex. The main function of histamine neurons is to maintain the brain in wakefulness mode, during periods of relaxation / fatigue, their activity decreases, and during REM sleep they are inactive.

Histamine has a protective effect on the cells of the central nervous system, it reduces the predisposition to seizures, protects against ischemic damage and the effects of stress.

Histamine controls the mechanisms of memory, contributing to the forgetting of information.

reproductive function

Histamine is associated with the regulation of sexual desire. Injection of histamine into the cavernous body of men with psychogenic impotence restored erections in 74% of them. It has been found that H2 receptor antagonists, which are usually taken in the treatment of peptic ulcer in order to reduce the acidity of gastric juice, cause loss of libido and erectile dysfunction.

Destruction of histamine

The histamine released into the intercellular space, after connecting with the receptors, is partially destroyed, but for the most part goes back to the mast cells, accumulating in the granules, from where it can be released again under the action of activating factors.

The destruction of histamine occurs under the action of two main enzymes: methyltransferase and diaminooxidase (histaminase).

Under the influence of methyltransferase in the presence of S-adenosylmethionine (SAM), histamine is converted to methylhistamine.

This reaction mainly occurs in the central nervous system, intestinal mucosa, liver, mast cells (mast cells, mast cells). The resulting methylhistamine can accumulate in mast cells and, upon leaving them, interact with H1 histamine receptors, causing all the same effects.

Histaminase converts histamine to imidazoleacetic acid. This is the main reaction of histamine inactivation, which occurs in the tissues of the intestine, liver, kidneys, skin, thymus cells, eosinophils and neutrophils.

Histamine can bind to certain protein fractions of the blood, which inhibits excessive interaction of free histamine with specific receptors.

A small amount of histamine is excreted unchanged in the urine.

Pseudo-allergic reactions

Pseudo-allergic reactions external manifestations are no different from true allergies, but they do not have an immunological nature, i.e. non-specific. With pseudo-allergic reactions, there is no primary substance - an antigen, with which a protein-antibody would bind into an immunological complex. Allergic tests with pseudo-allergic reactions will not reveal anything, because the reason for the pseudo-allergic reaction is not in the penetration of a foreign substance into the body, but in the intolerance of the body itself to histamine. Intolerance occurs when there is an imbalance between histamine, which enters the body with food and is released from cells, and its deactivation by enzymes. Pseudo-allergic reactions in their manifestations do not differ from allergic ones. These can be skin lesions (urticaria), spasm of the respiratory tract, nasal congestion, diarrhea, hypotension (low blood pressure), arrhythmia.

Often pseudo-allergic reactions occur when using products with high concentration histamine. Read more about histamine-packed foods.

Histamine is a compound that regulates various functions organism. It can be synthesized in cells or come from outside.

Sources

1. The amino acid histidine. Part of some products, it is the basis for the synthesis of histamine in connective tissue. It's called endogenous; is deposited in the form of granules in specialized cells (basophils or mast cells).
2. Food containing histamine. In this case, it is exogenous.
3. Histamine accumulation may also be observed in violation of the intestinal microflora, for example, with dysbacteriosis.

Responses

In cells, histamine is contained in a bound form. Under stress, tissue damage, the action of toxins, foreign agents, etc., it is released and becomes active, which is manifested by a number of reactions:

• spasms of smooth muscles,
• an increase in the amount of hydrochloric acid in the stomach,
• lowering blood pressure,
• extension peripheral vessels,
• mucus secretion,
• narrowing of the vessels of the pulmonary circulation,
• swelling of the skin, mucous membranes,
• hyperemia.

Histamine supplied with food and accumulated as a result of improper functioning of the intestine causes the same reactions in the body as the released endogenous one. Manifestations depend on which receptor the interaction occurs with.

There are 3 types of histamine receptors: H1, H2, H3. The first are located in smooth muscles, the membrane of blood vessels, the central nervous system. When binding to H1, the bronchial muscles, intestinal muscles, and blood vessels contract, and the production of prostaglandins increases. Receptors of this type lead to the accumulation of fluid around the vessels, causing edema and hives.

H2 receptors are found in the parietal cells of the stomach. Interacting with them, histamine causes an increase in the activity of the glands of the stomach, the formation of mucus. Simultaneous stimulation of H1 and H2 leads to the expansion of peripheral vessels and the onset of itching. H3 receptors located in the CNS and peripheral departments NS, suppress the release of serotonin, norepinephrine and other neurotransmitters.

Free histamine can be bound to blood proteins or inactivated by the enzymes methylhistamine and histaminase. This process occurs in the liver, connective tissue, placenta, kidneys. Inactivated, it is stored again in mast cells. A small amount is excreted in the urine.

Foods can directly cause the release of endogenous histamine, leading to the development of an allergic reaction, or they themselves are a source of its increased amount, causing food intolerance. In the latter case, histamine, entering the body, causes manifestations similar to true allergies.

The level of histamine in products is regulated by certain standards. Thus, according to Russian standards, its content in fish, for example, should not exceed 100 mg/kg.

The following products cause the activation of their own histamine:

• Strawberry,
• chocolate,
• alcohol,
• pig liver,
• egg white,
• wheat,
• shrimps,
• artificial additives (dyes, preservatives, etc.).

Foods containing histamine increased quantities, relate:

• sausages,
• beer,
• cheeses,
• sauerkraut,
• eggplant,
• tomatoes,
• canned foods.

The amount of histamine in products can increase significantly if they are not properly stored, violated the conditions of transportation, canned and frozen. After eating such food, responses to it may even be healthy people.

Since histamine is quickly inactivated, not very pronounced single manifestations can go away on their own. However, in the case of numerous and vivid reactions, it is necessary to take antihistamines (according to the instructions for use). Histamine poisoning can lead to suffocation, convulsions, and death.

Application in medicine

Histamine can be used to treat diseases, for research and diagnosis. When evaluating functional state stomach, a solution of histamine hydrochloride of a certain concentration is used. The goal is to stimulate the secretion of gastric juice.

As a drug, histamine is used in the following diseases:

• polyarthritis,
• myeloid leukemia,
• rheumatism,
• allergic reactions,
• radiculitis,
• pain of nervous origin.

Indications for the use of histamine are also migraine, urticaria, bronchial asthma.

Histamine as a medicine is used in the form of an ointment, injections, and is used in electrophoresis. Instructions for the drug Histamine contains a fairly extensive list side effects and contraindications, so its purpose and dosage should be under the supervision of a doctor.

In addition, in pharmacology there are preparations containing a combination of histamine with other active substances. For example, its combination with serum immunoglobulin () is indicated for use during the period of remission of allergic diseases. Such a complex increases the ability of the blood to inactivate free histamine.

For the treatment of allergies of various origins, the so-called dosed histamine immunotherapy is used. Its goal is the gradual development of insensitivity to a certain level of histamine in the blood. This approach makes it possible to select an individual amount of the drug and keep responses under control.

When allergies appear, you need to properly review your diet, paying attention to simple, natural products. It will not be superfluous to cleanse the body with herbs. It is necessary to monitor the intestines, which also depends on the food consumed. After all, it may well turn out that a banal refusal from sausages will return health and strength.

What is histamine and what is its role in the body? Histamine is a word familiar to those who have a pronounced tendency to allergic reactions and are forced to either lead a lifestyle that excludes allergens, or undergo treatment, that is, take antihistamines.

Histamine triggers various allergic reactions in our body - it is thanks to him that bronchospasm occurs, due to which a state similar to suffocation occurs, it causes tissue swelling. Why did nature endow human body this strange helper?

What is histamine in the body?

Histamine in pure form It is a colorless crystal that readily dissolves in water and ethanol. In the language of biochemists, its name sounds like this: 2-(4-imidazolyl)ethylamine.

In medicine, it is known as a neurotransmitter of allergic reactions. immediate type. And like any other neurotransmitter, histamine helps transmit electrical impulses from nerve cell to a neuron or from neurons to tissues. However, unlike other biologically active substances, it comes into action when an immediate reaction of our body to the penetration of a foreign antigen is required.

Imagine two divisions of the same corporation, one in Japan and one in Sweden. They cannot communicate without an interpreter. Any neurotransmitter is such a translator in the body - it transmits a signal between two links so that they work for the benefit of the entire system.

Alena Krotyuk

Where is histamine produced?

Histamine is produced from histidine, which resides in varying amounts in histiocytes (mast cells) in the tissues of the skin, lungs, and intestines.

Basically, histidine is an amino acid. It is part of the vast majority of proteins that we eat every day. In general, all huge protein molecules are built from only 20 different amino acids, and their properties depend on the order in which these amino acids line up in a chain.

Alena Krotyuk

Usually, histidine is in an inactive form, but under the influence of a number of factors, histamine begins to be released from mast cells, turning into an active form and provoking a number of the reactions described above. The release of free histamine is promoted by traumatic and thermal damage, stress reactions, ionizing radiation and, of course, allergic agents of food and drug origin.

However, in addition to endogenous histamine (that is, produced by the body), there is also exogenous (coming from outside). This neurotransmitter can be found in a number of foods, and most often it is found in those that are intended for long-term storage in refrigerators - sausages, cheeses (hard varieties). In addition, histamine is found in alcoholic beverages, and there is also a huge list allergenic products that stimulate the production of histamine in the body. The conclusion is simple: if you are prone to allergic reactions, the above products are best avoided.

Why is histamine dangerous?

Histamine acts on three groups of H receptors, causing three types of reactions.

The word "receptor" has many different reincarnations in the body, but the essence is always the same - it is a kind of receiver. When it comes to histamine and other mediators, we are talking about cell receptors. On the surface of each cell there is something like a combination lock, which only the necessary mediator can open and start the corresponding process. In this case, the allergic reaction is triggered by histamine. At its simplest, it looks like this:

1. an allergic person inhales ragweed pollen;
2. a foreign allergen protein triggers the release of histamine;
3. histamine "gains" its code on the cells of the smooth muscles of the bronchi;
4. smooth muscle cells contract, narrowing the lumen of the bronchi and causing suffocation.

Alena Krotyuk

H1 receptors localized in smooth muscles, endothelium, central nervous system. Influencing them, histamine provokes spasms of the bronchi, blood vessels, stimulates the pituitary gland.

H2 receptors located in parietal cells and exposure to them stimulates the production of gastric juice.

H3 receptors are located in the central and peripheral nervous system and exposure to them inhibits the release of GABA, acetylcholine, serotonin and norepinephrine. Due to the complex effect, histamine stimulates the production of adrenaline, which, in turn, affects the heart, increasing the pulse rate and blood pressure.

All this is necessary in order to block the spread of the allergen and evacuate it from the body as quickly as possible. However, with constant contact with the antigen, the protective potential of the body decreases and functional and morphological disorders develop on the part of internal organs and significantly reduced quality of life.

Alena Krotyuk

Thus, upon contact with plant pollen, mucosal edema develops and constant congestion nose, with prolonged contact with food and household allergens, allergic skin diseases can occur, bee stings and other insects can cause severe swelling.

And some of the reactions caused by histamine are themselves a threat to life. For example, anaphylactic shock, in which pressure drops sharply, loss of consciousness occurs, and even death is possible. And then the body already needs help in suppressing defensive reactions and, consequently, blocking the production of histamine itself.

The article was written jointly with Ekaterina Sizova and Alena Krotyuk.

Histamine is a very interesting substance, a kind of tissue hormone from the group of biogenic amines. Its main function is to raise the alarm in the tissues and throughout the body.

The alarm is raised if there is a real or illusory threat to life and health. For example, a toxin or an allergen. And this anxiety is very complex, multilevel and involves many systems of the body. Why are we interested in histamine?

Understanding the mechanisms of histamine metabolism will allow us to understand complex issues such as nerve allergies, many food intolerances, skin reactions to stress, stomach problems, and detoxification issues. Nowadays, the cause of many health problems is the excessive activity of histamine, which is the background against which many intolerances and disorders of the immune system develop. Excess can occur by various mechanisms, leading to complex complex impacts. At the same time, the person clearly feels unhealthy, but it is difficult to fit his complaint into the generally accepted classification of diseases.

Histamine on guard

By itself, histamine does not have a direct protective activity, its purpose is to create optimal conditions for the work of immune cells under stress. What conditions? Create puffiness, slow blood flow and activation of immune cells. Histamine is responsible for the rapid immune response fast development inflammation in a situation where microbes, viruses suddenly got into the body, or when you inadvertently poked yourself with a needle or got hurt with a knife. At that moment, when some foreign molecules began to penetrate into our body - it does not matter, bacteria or allergens - cells containing histamine react to this and begin to throw this substance into the intercellular environment. Most of the histamine accumulates in basophils or "mast cells", which are abundant in connective tissues. Now, if you rub your hand, it turns red. Why? The mechanical effect caused the release of histamine and the vessels dilated, so the skin turned red. Just? To roughly determine your histamine level, do a simple test. Roll up your sleeve and lightly scratch your arm from the wrist to the crook of the elbow (can be compared with several people). Within a minute, the scratch will turn red. This is due to the flow of histamine to the injured area. The higher the degree of redness and swelling, the higher the amount of histamine in your body. Accordingly, histamine triggers total inflammation, vasodilation, edema - we all know this primarily from allergic reactions, when something is not breathed in and it has already flowed from the nose, or the bronchi spasm, or the whole body itches.

Where is histamine located?

Under normal conditions, histamine is found in the body mainly in a bound, inactive state inside cells (basophils, mast cells, mast cells). There are many of these cells in loose fibrous connective tissue, and especially in places of potential damage - the nose, mouth, foot, internal surfaces of the body, blood vessels. Histamine, which is not derived from mast cells, is found in several tissues, including the brain, where it functions as a neurotransmitter. Another important site for the storage and release of histamine is the enterochromaffin-like cells of the stomach. Usually, histidine is in an inactive form, but under the influence of a number of factors, histamine begins to be released from mast cells, turning into an active form and provoking a number of the reactions described above.

HISTAMINE TOLERANCE TEST:

Rate Availability the following symptoms for the last 30 days. Use the scale below and mark on the right the frequency of symptoms that bother you: 0-Never; 1- Approximately once a month; 2- Approximately once a week; 3-daily; 4-Always

Gastrointestinal discomfort (bloating, diarrhea, etc.)

Skin symptoms (itching, redness, redness, rash)

Headache(including migraine and menstrual migraine), dizziness

mental fatigue

General discomfort

Panic attacks, sudden changes psychological state usually during or after a meal

"Lead exhaustion," usually during or after a meal ( increased drowsiness; however sleep does not restore vitality); General shortage energy

Chills, shivering, discomfort, difficulty breathing

Symptoms occur mainly after eating a specific food or drink

Your overall result to determine the approximate level of histamine intolerance.
1 - 10 Mild histamine intolerance
11 - 23 Moderate histamine intolerance
24 - 36 Severe histamine intolerance

How does histamine work?

In the body, there are specific receptors for which histamine is an agonist ligand (acts on receptors). Currently, there are three subgroups of histamine (H) receptors: H1-, H2- and H3-receptors. There are also H4 receptors, but they are still poorly understood.

H1 receptors

They are: smooth muscles, endothelium (internal lining of blood vessels), central nervous system. When activated, vasodilation (vasodilation), bronchoconstriction (narrowing of the bronchi, it is more difficult to breathe), spasm of the smooth muscles of the bronchi, expansion of endothelial cells (and, as a result, the passage of fluid from the vessels into the perivascular space, edema and urticaria), stimulation of the secretion of many hormones pituitary gland (including stress hormones).

Histamine has a pronounced effect on the integrity of postcapillary venules, causes an increase in vascular permeability, affecting H1 receptors on endothelial cells. This leads to local tissue edema and systemic manifestations. This often results in itching and small rashes. Also, in this case, there is a thickening of the blood and an increase in its coagulability, and in the tissues - swelling.

Histamine, released locally from mast cells, is involved in the onset of symptoms of allergic skin diseases (eczema, urticaria) and allergic rhinitis, and systemic release of histamine is associated with the development of anaphylaxis (shock). H1 receptor-related effects also include airway narrowing and smooth muscle contraction. gastrointestinal tract. Thus, histamine is associated with the occurrence of allergic asthma and food allergies.

H2 receptors

They are located in the parietal (parietal) cells of the stomach, their stimulation enhances the secretion of gastric juice. The effects of histamine caused by H2 receptors are less than those caused by H1 receptors. The majority of H2 receptors are located in the stomach, where their activation is part of the final effect leading to H+ secretion. H2 receptors are also found in the heart, where their activation can increase myocardial contractility, heart rate, and conduction in the atrioventricular node. These receptors are also involved in the regulation of the tone of the smooth muscles of the uterus, intestines, and blood vessels.

Together with H1 receptors, H2 receptors play a role in the development of allergic and immune responses. Through H2 - histamine receptors, the pro-inflammatory effects of histamine are realized. In addition, through H2 - receptors, histamine enhances the function of T-suppressors, and T-suppressors maintain immune tolerance.

H3 receptors

They are found in the central and peripheral nervous system. It is believed that H3 receptors, together with H1 receptors located in the CNS, are involved in neuronal functions associated with the regulation of sleep and wakefulness. Participate in the release of neurotransmitters (GABA, acetylcholine, serotonin, norepinephrine). The cell bodies of histamine neurons are found in the posterior lobe of the hypothalamus, in the tuberomammylar nucleus. From here, these neurons are carried throughout the brain, including the cortex, through the medial forebrain bundle. Histamine neurons increase alertness and prevent sleep.

Ultimately, H3 receptor antagonists increase alertness. Histaminergic neurons have a wakefulness-related firing pattern. They are rapidly activated during wakefulness, activated more slowly during periods of relaxation/tiredness, and completely cease to be activated during fast and deep phase sleep. Thus, histamine in the brain works as a mild excitatory mediator, that is, it is one of the components of such a system to maintain enough high level wakefulness.

It has been determined that histamine affects the processes of cortical excitability (sleep-wakefulness), the occurrence of migraine, dizziness, nausea or vomiting. central origin, changes in body temperature, memory, perception of information and regulation of appetite. It was shown that regardless of the time of day, the activity of migraine attacks decreased, which correlated with a decrease in the level of central histamine. In turn, an excess of histamine led to overexcitation of certain parts of the central nervous system, which caused various sleep disorders, including difficulty falling asleep. With an excess of histamine, a person is overexcited and has problems sleeping and relaxing.

Histamine and the brain

The tuberomamillary nucleus is the only source of histamine in the vertebrate brain. Like most other activating systems, the histaminergic system of the tuberomamillary nucleus is arranged according to a “tree-like” principle: very a small amount of neurons (in the rat brain - only 3-4 thousand, in the human brain - 64 thousand) innervates billions of cells of the new, ancient cortex and subcortical structures due to the colossal branching of their axons (each axon forms hundreds of thousands of branches).

The most powerful ascending projections are directed to the neurohypophysis, nearby dopamine-containing areas of the ventral tegmentum of the midbrain and the compact part of the substantia nigra, the basal region of the forebrain (large-cell nuclei of the innominate substance containing acetylcholine and gamma-aminobutyric acid(GABA)), striatum, neocortex, hippocampus, amygdala, and midline thalamic nuclei, and descending to the cerebellum, medulla oblongata, and spinal cord.

The interrelationships between the histaminergic and orexin/hypocretinergic systems of the brain are extremely important. The mediators of these two systems act synergistically, playing a unique role in maintaining wakefulness. Thus, it can be said that the histaminergic and other aminergic systems of the diencephalon, midbrain, and brainstem have a very significant similarity in their morphology, cellular and systemic physiology. Possessing multiple mutual connections, they form a self-organizing network, a kind of "orchestra", in which orexin (hypocretin) neurons play the role of a conductor, and histamine neurons play the first violin.

As you know, histamine is formed from the amino acid histidine, which enters the body with protein foods. Unlike histamine, histidine crosses the blood-brain barrier and is taken up by an amino acid transporter protein that transports it into the body of a neuron or varicose veins axon. Typically, the half-life of neuronal histamine is about half an hour, but it can be drastically shortened by exposure to external factors such as stress. Neuronal histamine is involved in many brain functions: maintaining brain tissue homeostasis, regulating some neuroendocrine functions, behavior, biorhythms, reproduction, body temperature and weight, energy metabolism and water balance, and in response to stress. In addition to maintaining wakefulness, brain histamine is involved in sensory and motor responses, emotional regulation, learning, and memory.

Hyperactive histamine

If you have chronic or episodic high histamine levels, then frequent problems will be next. Of course, they are not specific only to histamine, but they are worth paying attention to:

• Spasm of smooth (involuntary) muscles in the bronchi and intestines (this is manifested, respectively, by abdominal pain, diarrhea, respiratory failure)
• Multiple pseudoallergies to different products or for the same product of varying degrees of processing and storage
• Acid reflux and hyperacidity of the stomach
• Increased production of digestive juices and secretion of mucus in the bronchi and nasal cavity
• The impact on the vessels is manifested by the narrowing of large and the expansion of small blood paths, increasing the permeability of the capillary network. Consequence - swelling of the mucous membrane of the respiratory tract, hyperemia of the skin, the appearance of a papular (nodular) rash on it, pressure drop, headache
• Dizziness, fatigue, headaches and migraines
• Difficulty falling asleep, overexcited, but waking up easily
• Numerous food intolerances
• Often arrhythmias and cardiopalmus, unstable body temperature, unstable cycle.
• Frequent nasal congestion without infection, sneezing, difficulty breathing
• Excessive swelling of tissues, urticaria and vague rashes.

Symptoms of Histamine Excess

Acute and chronic histamine excess can be distinguished. Symptoms of acute excess are associated with ingestion of food that contains or provokes the release of histamine or with stress. A chronic increase in histamine is associated with a violation of the microflora, problematic methylation and increased formation of histamine, they are observed constantly and have an undulating course.

The severity of symptoms depends on the amount of histamine released. Symptoms of elevated histamine levels include gastrointestinal disturbances, sneezing, rhinorrhea, nasal congestion, headache, dysmenorrhea, hypotension, arrhythmia, urticaria, hot flashes, etc. clinical signs. Manifestations of elevated histamine are characterized by a dose-dependent effect. Even healthy people can develop severe headaches or hot flashes from eating large amounts of histamine-containing foods.

Scientists from the University of Granada, having analyzed the features of the occurrence and development of diseases such as fibromyalgia, migraine, chronic fatigue syndrome and others, found that many painful symptoms there may be one process, accompanied by high content histamine for a long time.

Symptoms such as pain different localization(muscular, articular, head), violation of thermoregulation, general weakness, dizziness, fatigue, unstable arterial pressure, stool disorder and others, can be caused increased concentration histamine in all tissues of the body. The researchers proposed to combine them into a group of diseases - central hypersensitivity syndrome, or chronic histamine syndrome. And, accordingly, the treatment of these conditions should include antihistamines - drugs that block histamine receptors.

Histamine and the nervous system

Neurological symptoms are manifested by headaches. It has been found that patients diagnosed with migraine have elevated histamine levels not only during attacks, but also during the asymptomatic period. In many patients, foods containing histamine were headache triggers

It is now known that histamine can cause, maintain, and exacerbate headache, although the mechanisms of this have not yet been fully established. It is believed that in some pathological conditions (migraine, cluster headaches, multiple sclerosis), the number of mast cells in the brain increases. Although histamine does not cross the blood-brain barrier (BBB), it can affect the activity of the hypothalamus. The study by Levy et al. confirmed that mast cell degranulation in the dura activates the pain pathway underlying migraine. However, most antihistamines ineffective at acute attack migraine.

Histamine and the gastrointestinal tract

Important symptoms are diffuse pain in the abdomen, colic, flatulence, diarrhea or constipation, often occurring as early as 30 minutes after a meal containing high doses or stimulating the release of histamine. An increase in the concentration of histamine and a decrease in the activity of enzymes that break down histamine have also been found in other diseases of the gastrointestinal tract (Crohn's disease, ulcerative colitis, allergic enteropathy, colorectal cancer). It is also important to note that the level of histamine in food can only be determined by special laboratory methods, it depends on the terms and conditions of storage of products. Freeze or hot processing does not reduce the content of histamine in food. The longer food is stored, the more histamine is formed in it. The same products may contain different amount histamine and, accordingly, cause (or not) varying degrees symptoms, making diagnosis difficult.

Respiratory tract and histamine

Excess histamine may be present in patients with atopic allergic diseases and without them. During or after drinking alcohol or foods rich in histamine, patients may experience symptoms such as rhinorrhea, nasal congestion, cough, shortness of breath, bronchospasm, and asthma attacks. It is these cases that are of great differential interest for competent and timely verification of the diagnosis.

skin and histamine

Most often, the skin manifests itself in the form of urticaria of various localization and severity against the background of the intake of food rich in histamine, or a reduced concentration of the enzyme when eating dietary food or medications that increase histamine metabolism. A decrease in the activity of enzymes that break down histamine has been found in patients with atopic dermatitis. Most of those described in the literature clinical cases this combination was accompanied by an increase in the severity of the course of dermatitis, especially in childhood. When following a histamine-restricted diet or taking medications replacement therapy relief of symptoms of atopic dermatitis was observed.

Cardiovascular system and histamine

Too much histamine affects cardiovascular system differently, which is associated with hyperactivation of H1 and H2 receptors located in the heart and blood vessels. This leads to the development of many different clinical symptoms, which veil the standard idea of ​​this disease. In particular, through interaction with vascular H1 receptors, histamine mediates their expansion with nitric oxide and prostaglandins (through endothelial cells); increases the permeability of postcapillary venules, resulting in edema; affects the contraction of the blood vessels of the heart. Through interaction with H2 receptors, it causes vasodilation mediated by cAMP (vascular smooth muscle cells). In addition, histamine contributes to a decrease in atrioventricular conduction through interaction with H1 receptors in the heart tissue, and also increases chronotropy and inotropy through an effect on the H2 receptors of the heart.

Reproductive system and histamine

Women with histamine intolerance often suffer from dysmenorrhea associated with cyclic headache. These symptoms are explained by the interaction of histamine and female sex hormones, in particular the ability of histamine to support uterine contractions. This is due to the fact that histamine, depending on the dose, stimulates the synthesis of estradiol and slightly - progesterone. Estradiol, in turn, has the ability to inhibit the formation of progesterone F2α, which is responsible for painful contractions uterus in dysmenorrhea. The intensity of symptoms may vary depending on the phase menstrual cycle, in particular, in the luteal phase, manifestations decrease, which is due to the high activity of the enzyme that breaks down histamine.

Pseudo-allergy and histamine

Many have heard about histamine, and those who have had the burden of allergies know this substance quite well. That is what is causing huge amount allergic reactions: from urticaria and food intolerances to Quincke's edema. Headache, redness of the face when drinking red wine, the desire to immediately take out a handkerchief at the mere sight of bananas, eggplants or citrus fruits - this is all he, histamine. And to be more precise, we can suspect histamine intolerance or histaminosis. True allergy is, first of all, a highly specific process, therefore, patients with true allergies are characterized by sensitization mainly to one antigen only.

If the patient notes intolerance to many foods, then, most likely, we are talking about the so-called pseudo-allergy, which is characterized by similar clinical manifestations. However, pseudo-allergic reactions occur without an immunological phase and therefore, in fact, are non-specific. Despite the prevailing opinion, allergies are quite rare in clinical practice. Basically, the clinician deals with a variety of manifestations of pseudo-allergic reactions, which are clinical analogues allergies, but requiring a completely different approach to treatment and prevention.

A variety of histamine pseudo-alleria is a nervous allergy. Nervous allergy is referred to as pseudo-allergy, since it occurs without the presence of an allergen - a substance that provokes the release of histamine. An elevated level of histamine in the blood is fixed, but skin tests do not detect the allergen during the dormant period. One has only to start to get nervous, as the meanings of previously unmanifested skin reactions are found to be positive.

Differences between true and pseudo-allergic reactions

sign
Allergic reactions true
Pseudo-allergic reactions

Atopic diseases in the family
Often
Rarely

Atopic diseases in the patient himself
Often
Rarely

Number of allergens causing a reaction
Minimum
Relatively large

The relationship between the dose of the allergen and the severity of the reaction
Not
There is

Skin tests with specific allergens
Usually positive
Negative

The level of total immunoglobulin E in the blood
Promoted
Within normal limits

Specific immunoglobulin E Detected
Missing

"Leaky Organs"

An increased level of histamine causes swelling of the tissues and significantly increases the permeability of capillaries at the site of exposure. The increase in permeability makes sense - for the release of immune cells. But the fact is that increased permeability can also be an entry gate for pathogens. Therefore, with chronic inflammation and an excess of histamine, “leaky organ” syndromes can form. We will talk about them in detail later, so far only in general terms.

So, a leaky gut (also known as leaky gut syndrome, leaky gut syndrome, or irritable bowel syndrome) is a damaged gut with large openings open, allowing large molecules such as food proteins, bacteria, and waste products to pass through those openings. The mechanisms that lead to a leaky gut can also cause leaky lungs. As in the gut, microbial communities are likely to have a significant impact on the integrity lung tissue. In contrast to the gut, however, a decrease in diversity appears to be associated with better health. Asthmatics have been shown to have a greater diversity of microbes in their lungs compared to healthy individuals.