What is histamine release? Histamine. Where is histamine located?

2-(1H-imidazol-4-yl)ethanamine

Properties:

Histamine is an organic nitrogen-containing compound that is involved in local immune responses and also regulates the physiological function of the intestines and acts as a neurotransmitter. Histamine is related to the inflammatory response. As part of the immune response to foreign pathogens, histamine is produced by basophils and mast cells found in nearby connective tissues. Histamine increases capillary leakage for white blood cells and certain proteins, allowing them to attack pathogens in infected tissues.

Properties

The histamine base, obtained as a homogeneous soft mass of mineral oil, melts at a temperature of 83-84 °C. Phosphorus hydrochloride and salts form white hydroscopic crystals that are readily soluble in water or ethanol, but not in ether. In aqueous solution, histamine exists in two tautomeric forms: Nπ-H-histamine and Nτ-H-histamine. The imidazole ring contains two nitrogen atoms. The nitrogen furthest from the side chain is the "tel" nitrogen and is represented by the lowercase tau sign. The nitrogen closest to the side chain is "pro" nitrogen and is represented by the sign pi. The position of the nitrogen with the hydrogen on it determines what the tautomer is called. If nitrogen and hydrogen are in the tele position, then histamine is presented in the form of a tele-tautomer. The tele-tautomer predominates in solution. Histamine has two main centers, namely the aliphatic amino group and any nitrogen atom of the imidazole ring that no longer has a proton. Under physiological conditions, the aliphatic amino group (has a pKa of about 9.4) will be protonated, while the second nitrogen of the imidazole ring (pKa ≈ 5.8) is not protonated. Thus, histamine is usually protonated to a singly charged cation.

Synthesis and metabolism

Histamine is produced from the decarboxylation of the amino acid histidine, a reaction catalyzed by the enzyme L-histidine decarboxylase. It is a hydrophilic vasoactive amine. Once formed, histamine is either stored or quickly deactivated by its primary degradative enzymes, methyltransferase or diamine oxidase. In the central nervous system, histamine released into synapses is predominantly broken down by histamine N-methyltransferase, although in other tissues both enzymes may be important. Several other enzymes, including MAO-B and ALDH2, further process proximate histamine metabolites for clearance and recycling. The bacteria are also capable of producing histamine using histidine decarboxylase enzymes, unrelated to those found in animals. A non-infectious form of foodborne illness, such as mackerel poisoning, is associated with the production of histamine by bacteria in spoiled food, particularly fish. Fermented foods and drinks naturally contain small amounts of histamine due to a similar conversion performed by fermenting bacteria or yeast. Sake contains histamine in the amount of 20–40 mg/l; wines contain it in amounts of 2–10 mg/l.

Storage and release

Most histamine in the body is produced in granules in mast cells and white blood cells called basophils and eosinophils. There are especially many mast cells 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 histamine storage and release is the enterochromaffin-like (ECL) cells of the stomach. The most important pathophysiological mechanism for the release of histamine by mast cells and basophils is the immunological mechanism. These cells, if sensitized by immunoglobulin E antibodies, attach to their membranes and degranulate when exposed to the corresponding antigen. Certain amines and alkaloids, including drugs such as morphine and curare alkaloids, can move histamine into the granules and cause its release. Antibiotics such as polymyxin also stimulate the release of histamine. Histamine release occurs when allergens bind to mast cell-bound immunoglobulin E antibodies. Reducing excess immunoglobulin E production may reduce the likelihood of detecting enough immunoglobulin E to trigger histamine release from mast cells.

Mechanism of action

Histamine exerts its effects by binding to G protein-coupled histamine receptors, designated H1 to H4. By binding to the H2 receptor, histamine is protonated in the final chain of the amino group. This amino group interacts with aspartic acid in the transmembrane domains of the receptor. Other nitrogen atoms interact with threonine and aspartic acid in various transmembrane domains; collectively this is referred to as the tri-pointed interaction. By placing transmembrane domains close to each other, it triggers a signal transduction cascade. It should be noted that all known physiological reactions of histamine are a series of weak interactions; the histamine base remains unchanged. Histamine receptors in insects such as Drosophila vulgaris are ligand-activated chloride channels that act to reduce neuronal activity. Histamine-activated chloride channels are involved in the transmission of peripheral sensory information in insects, especially in relation to light/vision perception. Two receptor subtypes have been discovered in Drosophila: HClA and HClB. There are no known G protein-coupled histamine receptors in insects.

Effect on the nasal mucous membrane

Increased vascular permeability leads to the fact that fluid from the capillaries is removed into the tissues, which causes the classic symptoms of an allergic reaction: a runny nose and watery eyes. Allergens can bind to immunoglobulin E-loaded mast cells in the mucous membranes of the nasal cavity. This can cause three clinical reactions:

sneezing due to histamine-mediated sensory neural stimulation

hypersecretion from glandular tissue

nasal congestion due to vascular congestion associated with vasodilation and increased capillary permeability

Roles in the body

Although histamine is less comparable to other biological molecules (containing only 17 atoms), it plays an important role in the body. It is related to 23 different physiological functions. Histamine is involved in many physiological functions because it has chemical properties that give it the ability to be versatile in binding. It is Coulombic (capable of carrying a charge), conformational and flexible substance. This allows him to interact and connect more easily.

Regulation of sleep and wakefulness

Histamine is released as a neurotransmitter. The cell bodies of histamine neurons are found in the posterior lobe of the hypothalamus, in the tuberomammillary 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. Typically, antihistamines (histamine H1 receptor antagonists) that cross the blood-brain barrier cause drowsiness. Newly developed antihistamines do not enter the brain and thus do not have this effect. Similar to the action of older antihistamines, destruction of histamine-releasing neurons or inhibition of histamine synthesis results in an inability to maintain activity. Ultimately, H3 receptor antagonists increase alertness. Histaminergic neurons have a wakefulness-related firing pattern. They activate rapidly during wakefulness, activate more slowly during periods of relaxation/fatigue, and completely cease to be activated during REM and deep sleep.

Release of gastric juice

Enterochromaffin-like cells located within the gastric glands release histamine, which stimulates nearby parietal cells by binding to the apical H2 receptor. Stimulation of parietal cells causes the absorption of carbon dioxide and water from the blood, which are then converted to carbon dioxide by the enzyme carbonic anhydrase. Inside the cytoplasm of the parietal cell, carbon dioxide immediately breaks down into hydrogen and bicarbonate ions. Bicarbonate ions cross back through the basilar membrane and enter the bloodstream, while hydrogen ions are drawn into the gastric lumen via the K⁺/H⁺ ATPase pump. Histamine release stops when the pH of the stomach begins to decrease. Antagonist molecules such as ranitidine block the H2 receptor and prevent the binding of histamine, causing a decrease in the secretion of hydrogen ions.

Protective action

While histamine has stimulatory effects on neurons, it also has inhibitory effects that protect against seizure susceptibility, drug sensitivity, hypersensitivity denervation, ischemic injury, and stress. Histamine has also been found to control the mechanisms by which memories and knowledge are forgotten.

Erection and reproductive function

Loss of libido and erectile failure may occur during treatment with histamine (H2) receptor antagonists such as cimetidine, ranitidine and risperidone. Injection of histamine into the corpus cavernosum in men with psychogenic impotence completely or partially restores erection in 74% of them. It has been shown that H2 antagonists may cause sexual difficulties by reducing testosterone uptake.

Schizophrenia

Levels of histamine metabolites are elevated in the cerebrospinal fluid of people with schizophrenia, while the efficiency of the active sites of H(1) receptors is reduced. Many atypical antipsychotic drugs act by reducing histamine production (antagonists), and for this reason their use in people with this disorder is considered inappropriate.

Multiple sclerosis

Histamine therapy for the treatment of multiple sclerosis is currently under research. Different H receptors have different effects on the treatment of a given disease. The H1 and H4 receptors were shown to be counterproductive in the treatment of multiple sclerosis in one study. H1 and H4 receptors are thought to increase the permeability of the blood-brain barrier, thereby increasing the infiltration of unwanted cells into the central nervous system. This can cause inflammation and the symptoms of multiple sclerosis worsen. The H2 and H3 receptors are thought to have beneficial effects in the treatment of patients with multiple sclerosis. Histamine promotes T cell differentiation. This is important because in multiple sclerosis, the body's immune system attacks its own myelin sheaths on nerve cells (causing loss of signaling function and possible nerve degeneration). By promoting T cell differentiation, T cells are less likely to attack the body's own cells and instead attack invaders.

Diseases

As an integral part of the immune system, histamine may be related to immune system diseases and allergic reactions. Mastocytosis is a rare disease in which there is a proliferation of mast cells that produce excessive amounts of histamine.

Story

The properties of histamine, when it was called β-iminazolylethylamine, were first described in 1910 by British scientists Henry G. Dale and P.P. Laidlaw. "H-substance" or "substance H" has been used from time to time in the medical literature to describe histamine or a hypothetical histamine-like diffusible substance released during allergic reactions by the skin or in response to tissue inflammation.

Many of us know that in case of allergies, the patient is prescribed medications that should eliminate the effect of a substance such as histamine. one of the neurotransmitters (mediators) that regulate important functions of the human body. Histamine is localized in all cells of the body and is inactive under normal conditions. When an allergen penetrates, it is activated and released into the blood in a large volume. The amount of this substance varies for each person.

How to determine histamine levels?

To find out the approximate content of this substance in the body, you can take a simple test. To do this, you need to lightly scratch your hand from the elbow to the wrist. After some time, the scratch will turn red. This suggests that histamine is supplied to the damaged area, which helps eliminate inflammation. The stronger the redness and swelling, the higher the histamine content in the body. If the skin changes are significant and do not disappear for a long time, it means that the person has increased histamine.

Its concentration must be reduced, since a high level of this substance in the blood can provoke this. This can be done with the help of a timely injection of adrenaline.

Histamine - what is it, and how to reduce its concentration in the body?

In order for the body to eliminate the undesirable properties of inflammation, it is necessary to reduce the concentration of histamine in the blood. This can be done with the help of a certain diet that excludes foods with a high content of this substance, such as:

alcoholic drinks (in particular red wine);
smoked products;
yeast;
seafood;
cocoa, coffee;
pickled vegetables and fruits;
Wheat flour;
citrus.

The following products are allowed:

milk, cottage cheese;
bread;
cereals;
sugar, vegetable oils;
fresh meat;
vegetables, with the exception of tomatoes, spinach, cabbage, pumpkin, eggplant.

Histamine as a medicine

So, we have learned a lot about histamine: what it is and what role it plays in the human body. But it turns out that this substance may be a cure. Indications for its use may include polyarthritis, migraine, muscle and joint rheumatism, radiculitis, and allergic reactions. In the latter case, the dose of histamine is gradually increased, thereby trying to achieve a more stable state of the body to various manifestations of allergies. However, there are a number of contraindications to taking this substance, these include:

heart disease;
dystonia;
hypotension;
hypertension;
respiratory tract diseases;
renal dysfunction;
pheochromocytoma;
pregnancy;
lactation period.

Taking histamine can cause side effects such as severe continuous headache, dizziness, fainting, cyanosis, diarrhea, convulsions, tachycardia, nervousness, difficulty breathing, nausea, vomiting, a sharp decrease in blood pressure, redness of the facial skin, blurred vision, pain in the chest, swelling of the injection site.

We hope that now you know the answer to the question: “Histamine - what is it?”

Histamine is a biologically active substance that is found in the body and has a number of effects, influencing receptors specific to it. It is an obligatory mediator of the development of inflammatory and allergic reactions, regulates the functions of organs and tissues. Due to its participation in pathological processes, drugs were invented that could control the effects of histamine on cells.

What is histamine

Histamine is a mediator that is formed from the amino acid histidine. In most tissues of the human body, it is in an inactive state and is activated during allergic diseases, injuries, burns, and frostbite. There are also substances that can remove histamine from cells and increase its level in the blood. They are called liberators.

The most famous are food products (strawberries, citrus fruits, chocolate, coffee, tomatoes, bananas, peanuts, fish, cabbage, sausages, etc.) and medicines (propaniside, phenobarbital, succinylcholine, tubocurarine, dextrans, morphine, polymyxin, etc. ).

Scheme of formation and formula of histamine:

Receptors and effects

To act on tissue, histamine needs to contact receptors that are found in different organs. Currently there are 3 subtypes - H-1, H-2, H-3:

Receptor type	Localization	Main functions and effects
H-1	Smooth muscles of the bronchi, intestines, arteries and veins. Capillaries, heart, postsynaptic neurons of the central nervous system	Dilatation of blood vessels and an increase in their permeability, which leads to swelling and a drop in blood pressure, narrowing of the bronchi and hypersecretion of mucus, acceleration of the heart rate, increased itching, stimulation of the release of pituitary hormones
N-2	Stomach, heart, smooth muscles of arteries and uterus. Mast cells, basophilic and neutrophilic leukocytes, lymphocytes, adipose tissue, neurons of the central nervous system	Increased gastric secretion, decreased vascular tone, inhibition of uterine contraction, inhibition of histamine release by mast cells and basophils, decreased anti-inflammatory function of neutrophils
N-3	central nervous system	Suppression of neurotransmitter release

What is a histamine reaction?

The interaction of histamine with its receptor and activation of the effects described above is called the histamine reaction. The essence of the process can be expressed in accessible language using the example of an allergic reaction with the participation of this mediator.

The main source of histamine are basophils, or mast cells, which contain many granules with it. On the surface of these cells there are type E immunoglobulins, so-called antibodies. In order for histamine to leave the cell and degranulation to occur, the antigen must attach to the antibody. In this case, the antigen is usually called an allergen.

After its first entry into the body, histamine release does not occur, since cells acquire sensitivity to these foreign molecules. In simple words, they are "preparing" for the next contact with her. When the allergen re-penetrates, basophil degranulation will occur.

After the mediator leaves the cell, it connects with receptors. Their stimulation causes corresponding effects, which cause the symptoms of allergic processes:

Redness, itching and swelling of the skin.
Sneezing, itching and thin, clear nasal discharge.
Shortness of breath, cough, difficulty breathing.
Watery eyes, itchy eyes and swelling of the eyelids.

A histamine reaction in response to the body’s contact with an allergen can provoke serious consequences in the form of anaphylactic shock. It is characterized by swelling of the tongue and larynx, as a result of which the airways are closed, which leads to death if immediate assistance is not provided.

Medicines

Histamine is rarely used as a medicine due to the high risk of side effects:

Can be used to reduce pain in articular and muscular rheumatism, polyarthritis, radiculitis, plexitis by intradermal administration of a solution of histamine dihydrochloride.
When assessing the functional state of the stomach, since it stimulates its secretion. However, now Pentgastrin or Bentazol are more often used for this.
For allergic diseases, bronchial asthma, and urticaria, intradermal injections of histamine can be prescribed with a gradual increase in dose. It is believed that the body develops resistance to it and reduces its susceptibility to allergic reactions.

Of more practical importance is the elimination of the effects of histamine in pathological processes. For this purpose, there is a group of antihistamines, which are classified according to their mechanism of action.

H1 receptor blockers are used for allergies:

1st generation - Diphenhydramine, Fenistil, Suprastin Diazolin, Tavegil, etc. (non-selectively block H-1, 2, 3 receptors, therefore they have the largest number of side effects).
2nd generation - Claritin, Lorano, Lorfast, Loratadine, etc. Selectively switch off H1 receptors.
3rd generation - Eden, Erius, Loratek, Tsetrin, Tsetrilev, etc. The greatest selectivity to the first subtype of receptors.

H2 receptor blockers are used for diseases of the gastrointestinal tract:

1st generation - Cimetidine.
2nd generation - Ranitidine.
3rd generation - Famotidine.
4th generation - Nizatidine.
5th generation - Roxatidine.

The concept of “histamine” is well known to those people who have had to deal with an allergic reaction to something in their lives and take antihistamines. Therefore, many people think that histamin is itself. However, this is a misconception.

What it is

Histamine was first synthesized in 1907. If we talk about a biological substance in its pure form, then it is a colorless crystal that can dissolve in water or ethanol.

In general, it is a mediator of allergic reactions. The secretion of this biologically active substance is histidine.

In the normal state, in which it is always found in the body, this component is contained in almost all cells. Science called it histiocyte. It is then that it is safe and does not cause any harm. If it is influenced by certain factors, it is able to become active and concentrate in the blood in large quantities.

At its core, it is a tissue hormone. Its main task is to report a problem in the body if there is a threat to health. The defense mechanism itself activates many systems. Therefore, knowledge of this system will help to understand the true causes of allergies caused by nervousness, intolerance to certain foods, and reactions to stressful situations.

Today, the cause of a number of problems is the excessive activity of this biological substance, against the background of which diseases develop and immunity decreases. At the same time, the person feels unwell, but there are no apparent reasons for this.

Histamine exhibits its activity if there are catalysts that provoke it to action. These factors include:

injuries;
burns;
frostbite;
stress;
irradiation;
adverse reaction from taking medications;

The presence of synthesized tissue hormone in the blood can be observed due to the consumption of certain foods. There is also a lot of it in frozen foods. At low temperatures, increased amounts of the substance appear in food products.

Biological effects and functions in the body

If a substance in an active state enters the blood, it has a strong effect on all human organs. Changes begin from its excess:

breathing becomes difficult, bronchial spasms are possible;
stomach upset occurs;
adrenaline is released, causing the heart rate to increase;
the digestion process is accelerated;
Blood pressure drops and headaches begin;
with a high concentration in the blood, anaphylactic shock can occur - the pressure drops sharply, the person loses consciousness, convulsions and vomiting are possible.

The main functions of the chemical, which interacts with almost all organs, are a number of important life processes:

Regulates blood supply to organs and tissues. If a person works physically hard, then a lack of oxygen may occur in the muscles. This is where histamine begins its work. It causes capillaries to dilate, which leads to increased blood flow and oxygen.
Regulates the acidity of the stomach, in the mucous membrane of which it acts as a mediator. Stimulates cells capable of producing hydrochloric acid.
Regulates inflammation in the body.
Nervous regulation. Histamine maintains the central nervous system in a state of wakefulness. During periods of relaxation or fatigue, the activity of histamine neurons decreases, and during short sleep they completely stop their activity. The biological substance also protects cells of the nervous system, prevents seizures, ischemic damage, stressful situations in the central nervous system and promotes forgetting of unnecessary information.
Regulates reproductive function and sexual desire. The introduction of a biological substance into the body of a man who had problems with erection restored it by three quarters. Therefore, if you reduce, for example, with the help of receptor antagonists, acidity in the stomach, you may encounter loss of libido or even impotence.

There are women who suffer from intolerance to this tissue hormone. This is due to its interaction with female hormones and the ability of the hormone to provoke uterine contractions.

Where does it come from in the body?

Scientists have long known that histamine is produced from histidine. In simple terms, histidine is an amino acid that is found in almost all protein foods. People use them every day. You need to understand that all protein molecules are built in a certain order from 20 different amino acids. And their properties will depend on the order in which they appeared.

It is worth noting that histamine resides in mast cells of human organs - skin, intestines and lungs.

Histamine and allergies

Histamine performs a special function during allergies. Here, in no case can it be done without two substances reacting with each other.

Antigen – the human body has already encountered it at some point. He remembered him and saved information about his “stay.” This substance had already entered the tissues and caused a certain irritability in the cells. All the information is already in the cells, but then antibodies react. And you need to understand that this becomes the main catalyst for the appearance of allergies.

Now that the body is familiar with the antigen, the antibodies begin to attack and neutralize it, merging together and getting to where the histamine is located in special granules.

This is the very initial stage of an allergic reaction. This is followed by the now active role of the biological substance. Histamine enters the active phase. After the immune complexes enter the mast cells, they begin to leave the granules and enter the blood. And if its concentration in the blood reaches a certain level, then the reactions described above begin. This is why histamine is confused with the cause of allergies. In fact, he is simply a conductor. Without it, it is difficult to imagine all the vital functions in the body.

Reactions that are very similar to allergies are also possible, but there is no tandem in the chain - antibody and antigen. This happens if an increased amount of biologically active substance enters the body with food.

Histamine receptors

Today, only three groups of specific histamine receptors have been studied.

More details about each:

H1. Receptors of this group are located in smooth muscles, in the lining of blood vessels from the inside and in the nervous system. These receptors are susceptible exclusively to external stimulation. Allergic reactions include bronchial spasms, gastrointestinal pain, swelling, and increased vascular permeability. The biological substance that has been released from mast cells is a conductor and contributes to the appearance of eczema, urticaria, and allergic rhinitis. The effects that receptors of this group have are narrowing of the lumen of the respiratory tract and contraction of muscles in the gastrointestinal tract. Therefore, we can say with confidence that the substance is involved in the occurrence of asthma and food allergies. Medicines that block receptors inhibit allergic reactions. Due to the fact that the process of this inhibition will occur in the brain, experts call drowsiness one of the side effects of these drugs. Therefore, people who work in jobs that require concentration should use these medications carefully. Drivers should especially pay attention to this fact.
H2. These receptors are located only in the cells of the stomach; if they are activated, the production of gastric juice - enzymes and hydrochloric acid - begins to increase. To block the receptors of this group, it is necessary to take drugs - cimetidine, roxatidine.
H3. Receptors of this group are located in the cells of the PNS. They are responsible for conducting impulses and regulating the period of sleep and wakefulness. If there is an excess, then a person has problems with sleep, excessive overexcitation and the impossibility of relaxation appear.

How is it dangerous for humans and how does it affect the body?

Of course, there is no clear answer to this question. Histamine is a substance without which the body will not function fully.

It is more dangerous when in excess. So, for example, if it comes into contact with flower pollen, swelling of the mucous membrane and nasal congestion may occur. If you come into contact with a large number of chemical allergens for a long time, it can cause skin diseases.

And there are reactions that are even dangerous to human life. Just look at anaphylactic shock – a sharp decrease in blood pressure, loss of consciousness. The body can be brought out of this state only by blocking the production of the substance.

Histamine destruction

Leaving its permanent habitat - mast cells, histamine is partially destroyed, but part of the substance is sent back, where it again accumulates in granules. Where it can come out again when activated.

It is destroyed only under the influence of several basic enzymes. The reaction occurs in the central nervous system, intestines and partly in mast cells.

Part of the substance is excreted from the body in the urine.

Pseudoallergic reactions

Such reactions, at first glance, similar to ordinary allergies, have nothing to do with an immunological nature. The main thing to understand here is that in the chain that is present in a true allergy, there is an antigen. And if a foreign organism is not detected in laboratory conditions, it means that there is an excess of a biologically active substance in the body - histamine.

It can be obtained from food, and at first glance it will seem to you that you are allergic to something - a skin rash, difficulty breathing, decreased blood pressure, arrhythmia, and upset stomach may appear. So in this case, foods rich in histamine should be consumed without enthusiasm.

Foods high in this organic compound:

strawberry;
hard cheese;
lemon;
a pineapple;
eggs;
tomatoes;
walnuts;
chocolate;
oranges.

Here is one of the striking examples. As a type of pseudo-allergy - nervous. It occurs without an allergen. All laboratory tests do not find the cause, and as soon as a person begins to get nervous, obvious signs of an allergy immediately appear. It occurs quite often.

The use of histamine in medicine

Very rarely, a patient is prescribed histamine-containing drugs for the treatment of rheumatism and certain neurological diseases.

Typically, with such appointments, an analysis is done to detect anaphylactic reactions.

Often it is necessary to reduce the level of histamine concentration in the body. Among the drugs that can do this is dihydrochloride. It is administered intramuscularly in small doses. Used for:

rheumatism, joint diseases, radiculitis;
allergic diseases.

However, it has a number of contraindications:

lactation period;
pregnancy.

If you choose the right dose and bring everything back to normal, you can get rid of diseases caused by high levels of this biological substance.

Difficult but important

It is important to understand how it works, what functions it performs and what effect this tissue hormone has on the body. It is already clear that it is involved in many processes occurring in the body. It is impossible to assess its harm or benefit. Because without it, a person simply will not be able to immerse himself in a very important physiological process - sleep.

However, most medical interventions are aimed at combating the undesirable effects of histamine.

Histamine is found primarily in some blood cells and in smaller amounts in the liver, kidneys, and intestinal wall. Histamine dilates blood vessels, reducing pressure, increases capillary permeability, causes contraction of the smooth muscles of the uterus, and stimulates the secretion of gastric juice rich in hydrochloric acid. Excess histamine is usually quickly eliminated from the body. Its accumulation leads to pathological phenomena. It is released from cells during allergic and anaphylactic reactions.

- anaphylactic reaction is an immediate allergic reaction, a sharply increased sensitivity of the body to an allergen, a very dangerous complication, in 10-20% of cases it ends in death.

The level of histamine in the blood determines the severity of anaphylactic and allergic reactions. Increased levels of histamine in the blood are also detected in cancer of the stomach and small intestine.

Histamine is an organic nitrogenous compound that is involved in local immune reactions, as well as in the regulation of physiological functions in the intestines and acts as a neurotransmitter (transmits nerve impulses). Histamine is involved in the inflammatory response and plays a central role as a mediator of itch. It accumulates in basophils and mast cells in an inactive (bound) state.

As part of the immune response to foreign pathogens, histamine is released by a number of high molecular weight compounds. It increases the permeability of capillaries to white blood cells and certain proteins to allow them to "take care" of pathogens in infected individuals.

There are three groups of histamine receptors - H1, H2 and H3. However, the H 4 receptor has also been identified on hematopoietic cells and in the central nervous system. Therefore, at present it is correct to talk about 4 groups of histamine receptors.

Synthesis and metabolism.

Histamine is formed by decarboxylation of the amino acid histidine in a reaction catalyzed by the enzyme L-histidine decarboxylase.

Once formed, histamine is either stored in basophils and mast cells or is quickly inactivated. The main degradation enzymes are histamine-N-methyltransferase and diamine oxidase. In the central nervous system, histamine is released at synapses and destroyed by histamine-N-methyltransferase, while in other tissues it is acted upon by both enzymes. There are several other enzymes, including MAO-B and ALDH2, to further process histamine metabolites for elimination or processing.

Bacteria are also capable of producing histamine using enzymes different from those used in humans and animals. An example is a non-infectious form of foodborne illness called mackerel poisoning due to the production of histamine by bacteria in spoiled food, particularly fish. Fermented milk products and drinks naturally contain small amounts of histamine as a result of fermentation by bacteria or yeast. Sake contains histamine 20-40 mg/l; wines contain it in the range of 2-10 mg/l.

The role of histamine in the body

Although histamine is a small molecule compared to other biological molecules (containing only 17 atoms), it plays an important role in the body. It is involved in 23 different physiological functions due to its chemical properties that allow it to be versatile. It carries an electrical charge, allowing it to interact and communicate easily.

Vasodilation and drop in blood pressure.

When administered intravenously, histamine causes the greatest dilation of blood vessels, and therefore causes a drop in blood pressure. This is a key mechanism in anaphylaxis.

Impact on the nasal mucosa.

An increase in vascular permeability causes an influx of fluid from the capillaries into the tissue, which leads to the classic symptoms of an allergic reaction: runny nose and watery eyes.

Regulation of sleep-wake state.

Histamine is released as a neurotransmitter. The cell bodies of histamine neurons are located in the posterior hypothalamus. From here, these neurons travel throughout the brain, including the cerebral cortex. Histamine neurons increase the duration of the waking phase and reduce the duration of sleep. Classic antihistamines (histamine H 1 receptor antagonists), which cross the blood-brain barrier, cause drowsiness. Newer generation antihistamines do not penetrate the brain and therefore do not have a drowsiness effect. Suppression of histamine synthesis results in an inability to maintain an alert state. Finally, H3 receptor antagonists increase the ability to maintain wakefulness.

Release of acid in the stomach.

Histamine stimulates nearby parietal cells (secreting hydrochloric acid) located in the gastric glands by binding to their H 2 receptors. Stimulation of parietal cells leads to the absorption of carbon dioxide and water from the blood, which is then converted to carbonic acid by the action of the enzyme carbonic anhydrase. Within the cytoplasm of parietal cells, carbon dioxide readily dissociates into hydrogen and bicarbonate ions. Bicarbonate ions diffuse back across the basilar membrane into the bloodstream, while hydrogen ions are pumped into the gastric lumen through the K+/H+ ATPase pump. The release of histamine stops when the pH of the stomach begins to decrease. Antagonist molecules such as ranitidine block histamine H2 receptors and prevent binding, causing a decrease in the secretion of hydrogen ions.

Protective effects.

While histamine has a stimulating effect on neurons, it also suppresses seizures, drug sensitivity, ischemic injury, and stress. It is believed that histamine regulates the mechanisms by which received information is forgotten.

Erection and sexual function.

Loss of libido and erectile failure may occur during treatment with histamine H2 receptor antagonists such as cimetidine, ranitidine, and risperidone. Injection of histamine into the corpus cavernosum in men with psychogenic impotence leads to full or partial erection in 74% of them. It has been suggested that histamine H2 receptor antagonists may cause impairment in sexual function due to decreased testosterone uptake.

Schizophrenia.

Histamine metabolites accumulate in the cerebrospinal fluid of patients with schizophrenia, while the effectiveness of histamine H 1 receptors is reduced. Many antipsychotic drugs have the effect of reducing histamine production (antagonists), as its use appears to be unbalanced in people with this disorder.

Multiple sclerosis.

Histamine therapy for the treatment of multiple sclerosis is currently being studied. Different H receptors are known to have different effects in treating this disease. H 1 and H 4 receptors are believed to increase the permeability of the blood-brain barrier, thereby increasing the entry of unwanted elements into the central nervous system. This can cause inflammation and worsening symptoms of multiple sclerosis. H 2 and H 3 receptors are considered useful in the treatment of patients with multiple sclerosis. Histamine has been shown to help with T cell differentiation. This is important because in multiple sclerosis, the body's immune system attacks its own myelin sheaths on nerve cells, causing a loss of signaling function. By helping T cells differentiate, histamine causes them to be less likely to attack the body's own cells instead of attacking pathogenic elements.