Physiological effects of catecholamines and their mechanism of action. What are catecholamines

Adrenal hormones adrenalin And norepinephrine under common name catecholamines are derivatives of the amino acid tyrosine.

The role of adrenaline is hormonal, norepinephrine is primarily a neurotransmitter.

Synthesis

It is carried out in the cells of the adrenal medulla (80% of all adrenaline), the synthesis of norepinephrine (80%) also occurs in nerve synapses.

Catecholamine synthesis reactions

Regulation of synthesis and secretion

Activate: stimulation of the splanchnic nerve, stress.

Reduce: hormones thyroid gland.

Mechanism of action

The mechanism of action of hormones varies depending on the receptor. The degree of receptor activity may vary depending on the concentration of the corresponding ligand.

For example, in adipose tissue when low concentrations of adrenaline, α 2 -adrenergic receptors are more active, with elevated concentrations (stress) – β 1 -, β 2 -, β 3 -adrenergic receptors are stimulated.

Adrenergic receptors located on pre- and postsynaptic membranes, on the cell membrane outside the synapse. Their types are unevenly distributed across different organs. In this case, an organ can have either receptors of only one type, or several types.
Terminal adrenergic effect depends

on the predominance of the receptor type in the organ/tissue,
on the predominance of the receptor type on a particular cell,
on the concentration of the hormone in the blood,
from the state of the sympathetic nervous system.

Calcium-phospholipid mechanism

when excited α 1 -adrenergic receptors.

Adenylate cyclase mechanism

when activated α 2 -adrenergic receptors adenylate cyclase is inhibited,
when activated β 1 - and β 2 -adrenergic receptors adenylate cyclase is activated.

Targets and effects

α1-Adrenergic receptors

When excited α1-adrenergic receptors happens:

1. Activation glycogenolysis and gluconeogenesis in the liver.
2. Reduction smooth muscles

ureters and sphinter of the bladder,
prostate gland and pregnant uterus,
radial muscle of the iris,
lifting hair
spleen capsules.

3. Relaxation smooth muscles of the gastrointestinal tract and contraction of its sphincters,

α2-Adrenergic receptors

When excited α2-adrenergic receptors happens:

decline lipolysis as a result of decreased stimulation of TAG lipase,
suppression insulin secretion and renin secretion,
spasm blood vessels V different areas bodies,
relaxation intestinal smooth muscles,
stimulation platelet aggregation.

β 1-Adrenergic receptors

Excitation β1-adrenergic receptors(present in all tissues) manifests itself mainly:

activation lipolysis,
relaxation smooth muscles of the trachea and bronchi,
relaxation smooth muscles of the gastrointestinal tract,
increase in the strength and frequency of myocardial contractions ( foreign- And chronotropic Effect).

β 2-Adrenergic receptors

Excitation β2-adrenergic receptors(present in all tissues) manifests itself mainly:

1.Stimulation

glycogenolysis and gluconeogenesis in the liver,
glycogenolysis in skeletal muscles,

2. Increased secretion

insulin,
thyroid hormones.

3.Relaxation smooth muscles

trachea and bronchi,
gastrointestinal tract,
pregnant and non-pregnant uterus,
blood vessels in different areas of the body,
genitourinary system,
spleen capsules,

4. Gain contractile activity of skeletal muscles ( tremor),

5. Suppression release of histamine from mast cells.

In general, catecholamines are responsible for biochemical adaptation reactions to acute stress, evolutionarily associated with muscle activity - "fight or flight":

gain products fatty acids in adipose tissue for muscle function,
mobilization glucose from the liver to increase the stability of the central nervous system,
maintaining energy needs of working muscles due to incoming glucose and fatty acids,
decline anabolic processes through a decrease in insulin secretion.

Adaptation can also be seen in physiological reactions:

brain– increased blood flow and stimulation of glucose metabolism,

muscles– increased contractility,

the cardiovascular system– increase in the strength and frequency of myocardial contractions, increase blood pressure,

lungs– dilation of the bronchi, improved ventilation and oxygen consumption,

leather– decreased blood flow,

Gastrointestinal tract And kidneys– decreased activity of organs that do not help the task of urgent survival.

Pathology

Hyperfunction

Tumor of the adrenal medulla pheochromocytoma. It is diagnosed only after the manifestation of hypertension and treated by removal of the tumor.

Introduction

Like the posterior lobe of the pituitary gland, the adrenal medulla is a derivative of nervous tissue. It can be considered a continuation of the sympathetic nervous system, since the preganglionic fibers of the splanchnic nerve terminate on the chromaffin cells of the adrenal medulla.

These cells got their name because they contain granules that turn red with potassium bichromate. Such cells are also found in the heart, liver, kidneys, gonads, postganglionic neurons of the sympathetic nervous system and in the central nervous system.

When the preganglionic neuron is stimulated, chromaffin cells produce catecholamines - dopamine, epinephrine and norepinephrine.

In most animal species, chromaffin cells secrete primarily epinephrine (~80%) and to a lesser extent norepinephrine.

By chemical structure catecholamines are 3,4-dihydroxy derivatives of phenylethylamine. The immediate precursor of hormones is tyrosine.

adrenal gland catecholamine brain hormone

Synthesis and secretion of catecholamines

The synthesis of catecholamines occurs in the cytoplasm and granules of cells of the adrenal medulla (Fig. 11-22). Catecholamines are also stored in the granules.

Catecholamines enter granules by ATP-dependent transport and are stored in them in complex with ATP in a 4:1 ratio (hormone-ATP). Different granules contain different catecholamines: some contain only epinephrine, others contain norepinephrine, and others contain both hormones.

Secretion of hormones from granules occurs by exocytosis. Catecholamines and ATP are released from the granules in the same ratio in which they are stored in the granules. Unlike sympathetic nerves, cells of the adrenal medulla lack a mechanism for reuptake of released catecholamines.

In blood plasma, catecholamines form a fragile complex with albumin. Epinephrine is transported mainly to the liver and skeletal muscles. Norepinephrine is formed mainly in organs innervated sympathetic nerves(80% of the total). Norepinephrine reaches peripheral tissues only in small quantities. T1/2 of catecholamines - 10-30 s. The main part of catecholamines is quickly metabolized in various tissues with the participation of specific enzymes. Only a small portion of adrenaline (~5%) is excreted in the urine.

The mechanism of action of catecholamines has attracted the attention of researchers for almost a century. Indeed, many general concepts receptor biology and hormone action go back to very early research.

Catecholamines act through two main classes of receptors: α-adrenergic and β-adrenergic. Each of them is divided into two subclasses: respectively and. This classification is based on the relative order of binding to the various agonists and antagonists. Epinephrine binds to (and activates) both α and β receptors, and therefore its effect on tissue containing both classes of receptors depends on the relative affinity of these receptors for the hormone. Norepinephrine in physiological concentrations binds mainly to α-receptors.

b-Adrenergic receptor

Molecular cloning of the mammalian α-adrenergic receptor gene and cDNA revealed unexpected features. Firstly, it turned out that this gene does not have introns and, therefore, together with the histone and interferon genes, it constitutes the only group of mammalian genes lacking these structures. Secondly, it was possible to establish that the β-adrenergic receptor has close homology with rhodopsin (at least in three peptide regions), a protein that initiates the visual response to light.

Table 49.2. Effects mediated by different adrenergic receptors

Mechanism of action

The receptors of three of these subgroups are associated with the adenylate cyclase system. Hormones that bind to β and P2 receptors activate adenylate cyclase, while hormones associated with α2 receptors inhibit it (see Fig. 44.3 and Table 44.3). Binding of catecholamines induces condensation of the receptor with the G-protein binding GTP gene. This either stimulates (Gs) or inhibits (GJ adenylate cyclase, resulting in increased or inhibited synthesis with AM P. The reaction is turned off when GTPa3a, bound to the G protein α subunit, hydrolyzes GTP (see Fig. 44.2) α,-Receptors are involved in processes leading to changes in intracellular calcium concentration or changes in phosphatidylinositide metabolism (or both), and it is possible that a special G-protein complex is required for this reaction.

There are functional similarities between the catecholamine receptor and the visual response system. Upon light stimulation, rhodopsin pairs with transducin, a G-protein complex, the α-subunit of which also binds GTP. Activated G protein in turn stimulates phosphodiesterase, which hydrolyzes cGMP. As a result, the ion channels in the membrane of the retinal cone cells close and a visual response occurs. It turns off when the α-subunit-associated GTPa3a hydrolyzes bound GTP. A partial list of biochemical and physiological effects mediated by various adrenergic receptors is given in Table. 49.2.

Activation of phosphoproteins by cAMP-dependent protein kinase (see Fig. 44.4) is responsible for many of the biochemical effects of adrenaline. In muscle and to a lesser extent in the liver, adrenaline stimulates glycogenolysis by activating protein kinase, which in turn activates the phosphorylase cascade (see Fig. 19.7). Phosphorylation of glycogen synthase, on the contrary, weakens glycogen synthesis. Acting on the heart, adrenaline increases minute volume as a result of increased strength ( inotropic effect) and frequency (chronotropic effect) of contractions, which is also associated with an increase in cAMP content. In adipose tissue, adrenaline increases the content of cAMP, under the influence of which hormone-sensitive lipase is converted into an active (phosphorylated) form. This enzyme enhances lipolysis and the release of fatty acids into the blood. Fatty acids are used as a source of energy in muscles and, in addition, can activate gluconeogenesis in the liver.

The main hormonoid catecholamines (adrenaline and norepinephrine) in to a large extent are produced by chromaffin tissue of an animal organism (the name of this specialized tissue is due to its coloration with chromium salts in a brownish-brown color). Chromaffin cells consist of the adrenal medulla, paraganglia located near the sympathetic nodes, and chains of special formations near abdominal aorta and in the area where the inferior mesenteric artery originates from it.

Another important site for the formation of these catecholamines is the organ synapses of the sympathetic nervous system and some parts of the brain. Dopamine is a catecholamine hormonoid of the hypothalamus (lactostatin).

In 1939, Blashko suggested that the initial substrates for the biosynthesis of catecholamines are phenylalanine or tyrosine. According to the hypothesis, they are converted first into dioxyphenylalanine (DOPA), then DOPA into dopamine, norepinephrine is synthesized from dopamine, and adrenaline is synthesized from it. Subsequently, the hypothesis was fully confirmed experimentally. Enzymes involved in the biosynthesis of catecholamines have also been identified:

As shown above, phenylalanine, when oxidized at the 4th position of the benzene ring, can easily be converted into tyrosine (hydroxyphenylalanine). Tyrosine, formed from phenylalanine or pre-existing in the cell, undergoes hydroxylation at the 3rd carbon atom of the ring in the soluble part of the cytoplasm to form DOPA. This stage of biosynthesis is a narrow (limiting) link in the process and is controlled by a special enzyme, tyrosine hydroxylase, in the presence of NADPH, O2 and tetrahydropteridine as a cofactor. Tyrosine hydroxylase is activated by Fe2+ ions and ammonium sulfate. Next stage formation of catecholamines - decarboxylation of DOPA, which results in the formation of dioxyphenylalanineamine (dopamine).

This stage is controlled by the cytoplasmic enzyme DOPA decarboxylase, which apparently acts in the presence of the cofactor pyridoxal-5'-phosphate. Dopamine synthesized in the soluble part of the cytoplasm passes further into the secretory granules of chromaffin or sympathergic cells, where it attaches enzymatically to the side chain in the position of the hydroxyl group, turning into norepinephrine.

The conversion of dopamine to norepinephrine occurs in the presence of atmospheric oxygen and ascorbic acid under the action of the enzyme dopamine β-hydroxylase (phenylethylamine β-oxidase), activated by Cu2+. This enzyme has a wide range of substrate specificity and is capable of hydroxylating a number of biogenic amines. If the biosynthesis of norepinephrine is carried out in special norepinephrine granules, then the process stops at this stage, and the resulting hormone can be secreted.

However, norepinephrine can also be transported into special adrenaline granules, where it is converted into adrenaline. The process of converting norepinephrine into adrenaline is reduced to the replacement of the hydrogen atom of the amino group with a methyl radical and is carried out using the enzyme phenylethanolamine-N-methyltransferase. This enzyme is found primarily in special adrenaline granules of catecholamine-producing cells. To carry out the process of methylation of norepinephrine, the amino acid methionine is also required as a donor of the methyl radical and ATP as an activator of its transport.

In this case, first, ATP in the presence of Mg2+ ions interacts with methionine, forming the activated form of the amino acid S-adenosylmethionine, after which the methyl radical is transferred by N-methyltransferase from the S-adenosylmethionine molecule to the norepinephrine molecule. Thus, the intensity of adrenaline formation depends, on the one hand, on the level of norepinephrine biosynthesis, on the other, on the reserves of methionine methyl groups. The system that ensures the methylation of norepinephrine, and therefore the intensity of adrenaline biosynthesis, is represented differently in different catecholamine-producing cells.

Yes, sympathergic nerve cells have low level activity of the methylation system and form predominantly norepinephrine, the main sympathetic transmitter (Euler, 1956). As nerve transmitter Some brain cells may also produce dopamine. At the same time, the adrenal glands in many species have a large number of cells that contain adrenaline granules rich in the methylation system. As a result, the adrenal glands produce large amounts of adrenaline, which serves as the main hormonoid of the glands in a number of animals.

Thus, in the human adrenal glands, adrenaline accounts for an average of 83% of all catecholamines; in the adrenal glands of rabbits and guinea pigs- more than 95%, cows - 80%. In cats, equal amounts of adrenaline and norepinephrine are noted in the gland, and in whales and poultry norepinephrine significantly predominates, reaching 80% of all catecholamines. The ratio of adrenaline to norepinephrine in chromaffin cells can have significant physiological significance, since their biological effects are largely different.

The biosynthesis of catecholamines in the adrenal medulla is directly regulated by nerve impulses arriving along the splanchnic nerve (Cheboksarov, 1910). One might think that neural regulation biosynthetic processes are carried out mainly at the tyrosine hydroxylase stage (the limiting link in biosynthesis), as well as at the stages of dopamine decarboxylation and norepinephrine methylation.

Corticosteroids and insulin take a certain part in the regulation of biosynthetic processes. Catecholamines themselves inhibit the activity of tyrosine hydroxylase and thereby participate in the self-regulation of biosynthetic processes.

All higher forms human behavior is related to normal life activities catecholaminergic cells - nerve cells that synthesize catecholamines and use them as a mediator. The activity of synthesis and release of catecholamines determines such complex processes, such as remembering and reproducing information, sexual behavior, aggressiveness and search response, level of mood and activity in the struggle of life, speed of thinking, emotionality, level of general energy potential, etc. The more active the synthesis and release of catecholamines is in quantitative terms, the higher the mood, general level activity, sexuality, speed of thinking, and simply efficiency.

Most high level catecholamines (per unit body weight) in children. Children differ from adults primarily in their very high emotionality and mobility, the ability to quickly switch thinking from one object to another. In children exclusively good memory, Always good mood, high learning ability and tremendous performance.

With age, the synthesis of catecholamines both in the central nervous system and in the periphery slows down. Tom has different reasons: this is aging cell membranes, and exhaustion of genetic reserves, and a general decrease in protein synthesis in the body. As a result of a decrease in the speed of thought processes, emotionality decreases and mood decreases. With age, all these phenomena worsen: emotionality and mood decrease, and cases of depression are common. The reason for this is one thing - an age-related decrease in the synthesis of catecholamines in the body. Why does performance directly depend on the amount of catecholamines in nerve cells?

Catecholamines have a mobilizing effect on the energy reserves of nerve cells. They activate redox processes in the body, “trigger” the combustion of energy sources - first of all carbohydrates, then fats and amino acids.

Catecholamines increase the sensitivity of cell membranes to sex hormones and somatotropin. Without having an actual anabolic effect, they enhance protein synthesis by increasing the sensitivity of cells to anabolic factors. Catecholamines directly or indirectly increase the activity of the endocrine glands, stimulate the hypothalamus and pituitary gland. With any strenuous work, especially physical work, the content of catecholamines in the blood increases. This is an adaptive reaction of the body to any kind of stress. And the more pronounced the reaction, the better body adapts, the faster the state of fitness is achieved. With intense physical work increased heart rate, increased body temperature (subjectively felt as heat in the body and perspiration) - all this is caused by nothing more than the release into the blood large quantity catecholamines.

The main types of catecholamines in the body are represented by three compounds:

1. Adrenaline;

2. Norepinephrine;

3. Dopamine.

Adrenalin, a substance produced by the adrenal glands. It is often called the “fear hormone” due to the fact that when frightened, the heart often begins to beat due to the strong release of adrenaline into the blood. This, however, is not entirely true. Adrenaline release occurs whenever strong excitement or heavy physical activity. Adrenaline increases the permeability of cell membranes to glucose and enhances the breakdown of glycogen and fats. If a person is scared or excited, then his endurance increases sharply. Adrenaline is an active doping human body. The greater the adrenaline reserves in the adrenal glands, the higher the physical and mental performance.

Unlike adrenaline, norepinephrine called the hormone of rage, because As a result of the release of norepinephrine into the blood, an aggressive reaction always occurs. Adrenaline causes a person's face to turn pale, and norepinephrine turns it red. Gaius Julius Caesar selected into his army only those warriors whose faces turned red in battle. This indicated the increased aggressiveness of such soldiers. If adrenaline mainly increases endurance, then norepinephrine significantly increases muscle strength.

High content in the nervous system dopamine enhances all sexual reflexes and increases the sensitivity of cells to sex hormones, which contributes to high anabolism. The most high content dopamine levels in the central nervous system differ among adolescents. Their mood has a touch of euphoria, and their behavior is marked by pronounced hypersexuality. Any training, even incorrect from a methodological point of view, in adolescence gives a good anabolic effect. Age drop dopamine content causes age-related depression (decreased mood), falling sexual activity(in men) and slowing down the rate of anabolic reactions.

Catecholamines realize the energy potential of the body. If the body's energy reserves are depleted, the release of catecholamines leads to even greater exhaustion and even death.

The realization of the body's energy potential occurs primarily due to the breakdown of liver glycogen depots and, secondly, due to muscle glycogen. The breakdown of muscle glycogen leads to a significant increase in muscle strength, and the mobilization of liver glycogen storage increases short-term endurance. Further release of catecholamines enhances the release of fatty acids into the blood from subcutaneous fat depots, and fatty acids are a practical “inexhaustible” source of energy in the body.

Catecholamines increase neuromuscular conduction, increase reaction speed and speed of thinking.

Even a superficial acquaintance with the metabolism of catecholamines in the body helps us to conclude that catecholamines are a key link in both mental and physical performance, both in speed and in the quality of thinking. Creative skills, the ability for abstract and artistic thinking, analysis and synthesis directly depends on catecholamine metabolism.

Analyzing the lives of great people: politicians, scientists, musicians, artists, etc., one can note amazing features. For example, a disease such as gout occurs almost 200 times more often among them than among ordinary people. The main mechanism of gout is the accumulation of uric acid in the blood. Uric acid has the ability to stimulate catecholamine receptors, increasing the sensitivity of cells to catecholamines. People with gout therefore have a lively character and high mobility of thinking.

The stimulating effect of drinks such as tea and coffee is very similar to the stimulating effect of uric acid, because these drinks affect the same receptors as uric acid. Alkaloids in tea and coffee “trigger” the synthesis of a special enzyme – adenylate cyclase. Adenylate cyclase leads to the accumulation of c-AMP (cyclic adenosine monophosphate) in cells. It changes the mechanism of the cell, increasing its sensitivity to catecholamines. The only trouble is that regular consumption of tea and coffee depletes the c-AMP reserves in the cell and ultimately depletes the nervous system. For this reason, tea and coffee cannot be recommended as sports stimulants. Among people with outstanding abilities, ten times more often than among ordinary people, there are people with increased thyroid function. And this is also not surprising, because thyroid hormones dramatically simulate the synthesis of catecholamines in the body and increase the sensitivity of cells to them. Almost all great people have such a quality as hypersexuality. Historians especially often pay attention to this. Sex hormones are able to replace catecholamine receptors and thereby have an activating effect on the central nervous system.

As we see, everything ultimately comes down to catecholamines: gout, increased thyroid function and increased activity gonads. Such a recognized genius as Alexander Sergeevich Pushkin had a combination of all three of the above factors. He suffered from hereditary gout, which he combated with daily cold ice baths. Because of increased function thyroid gland, he had extremely high physical and intellectual activity and never slept more than 5-6 hours a day. As for the love affairs of Alexander Sergeevich, they are all known and do not need comments.

Catecholamines stimulate physical activity to the same extent as intellectual activity. The same A.S. Pushkin was an excellent athlete: he swam a lot, fencing, boxing, etc.

Not only uric acid, thyroid hormones and sex glands activate the synthesis of catecholamines. There are many diseases, and it’s just hereditary factors, as a result of which catecholamines are produced in increased quantities, but all these factors are relatively rare.

Modern pharmacology has achieved a lot; with its help we can intervene both in the synthesis of individual catecholamines and in the activity of the entire sympathetic-adrenal system1 as a whole. By increasing the activity of catecholamine systems, we can achieve such an increase in athletic performance that we could only dream of before.

Almost all currently known catecholamines are classified as doping agents. Not only substances such as adrenaline, paradrenaline and dopamine are considered doping. Almost all sympathomimetic substances are classified as doping2. The best known sympathomimetics are amphetamines. Amphetamines significantly increase endurance and are used especially widely in sports where both endurance and reaction speed are required (for example, boxing).

Ephedrine, a plant alkaloid obtained from ephedra horsetail, is also a very popular doping. Ephedrine is extremely popular among bodybuilders because... it burns very well adipose tissue, but at the same time “does not touch” the muscles. Sympathomimetics generally differ in that, without having an actual anabolic effect, they increase the post-workout release of somatotropin and androgens into the blood, i.e. potentiate the physiological effect of training on the body.

There is no doubt that any sympathomimetic in large, ultra-high dosages can be harmful and can cause depletion of the nervous system.

The problem with sympathomimetics is generally not as simple as it seems. It is simply impossible to ban their use in sports, if only because many drugs stay in the blood for only a few tens of minutes, and the effects they have already caused physiological effects last for hours. Some catecholamines, strange as it may seem, at first glance in small doses have an anabolic effect, promoting the growth muscle mass and strength.

Adrenaline is considered a classic catecholamine. IN Lately a number appeared scientific works, in which the anabolic and general health-improving effect of small doses of adrenaline (1/10-1/20 from to, causing stimulation) has been proven. If large doses of adrenaline (from 1 ml and above) cause palpitations, a rise in blood sugar, an increase in blood pressure and the breakdown of glycogen in glycogen depots, then its doses can act in exactly the opposite way. The pulse slows down, blood pressure decreases, blood sugar drops and with prolonged course application a clear anabolic effect develops. Naturally, the use of such small doses does not give any stimulating effect and there can be no talk of any doping effect.

There are different types of sympathomimetics. In some of them, even in relatively large doses, the stimulating effect is weakly expressed, but the anabolic effect is quite strong. IN last years wide use in sports I received such a drug as clenbuterol. This is a synthetic catecholamine that has no analogues in nature. This drug is used to treat bronchial asthma, as well as for some types of shortness of breath, both pulmonary and cardiac origin. As soon as clenbuterol entered medical practice, it immediately began to be widely used in sports and it turned out that in addition to the stimulating effect, it has a pronounced anabolic effect, comparable to the effect anabolic steroids. Clenbuterol, moreover, does not cause pronounced palpitations, central nervous system stimulation, or an increase in blood pressure like other synthetic catecholamines.

The action of clenbuterol is very peculiar. Like small doses of adrenaline, small doses of clenbuterol have a distinct restorative and anabolic effect. In this case, a clear anti-inflammatory and antiallergic effect of the drug is manifested. Like some other catecholamines, clenbuterol improves sexual function in men and slightly improves mood. However, it must be noted that medical commission The IOC classified clenbuterol as a doping agent.

As we already know, with age the content of catecholamines in the central nervous system decreases due to genetic reasons, and due to the depletion of reserves (depot) of catecholamines in nerve cells. Each nerve cell from catecholaminergic structures has a certain reserve (depot) of catecholamines.

During severe stress(including during heavy physical exertion) there is a massive release of catecholamines from the depot. Sometimes such a release reaches such levels that the catecholamine depot is depleted and the nerve cell itself can no longer make up for their deficiency. There is nothing worse than depletion of catecholamines in the central nervous system. Previously, in medicine there was such a term as “exhaustion of the nervous system.” Nowadays such depletion is called “depletion of the sympathetic-adrenal system” and refers to the depletion of catecholamine depots in nerve cells. With such exhaustion, the body fades away literally before our eyes.

Every conceivable and unimaginable disease falls upon a person. He is getting old quickly. This rapid decline is due to the fact that much in the body depends on the regulatory role of catecholamines. Even self-renewal of cell membranes (subcellular molecular level!) is impossible without sufficient catecholamines in the body. Under the control of adrenaline and some other substances, phospholipid molecules constantly “enter” and “exit” cell membranes, carrying out their “current repair”. The stability of cell membranes and the viability of the cell, its resistance to all external (and internal too) damaging factors depend on the intensity and usefulness of such ongoing repairs.

Conclusions:

1. Severe stress (including excessive physical exercise) reduce the content of catecholamines in the central nervous system. To ensure that the reserves of catecholamines in the central nervous system are not depleted, it is necessary to train properly (not overtrain1) and recover correctly after exercise. Any competition is characterized by maximum mobilization of catecholamine reserves and their depletion. Therefore, it is very important to be able to prevent this depletion, to restore spent reserves, otherwise sooner or later they will be completely depleted, and then you will have to leave the sport.

2. Restoring CNS reserves without rational drug therapy is impossible. To deny this is to be hypocritical. Moreover, modern training loads big sport so great that they themselves constitute a serious debilitating factor. Rehabilitation treatment may be required not only in the inter-competition periods, but even in the inter-training periods. There are several ways to restore catecholamine reserves in nerve cells:

1. Administration of small doses of catecholamines;

2. Introduction of catecholamine precursors into the body;

3. Drugs that enhance the synthesis of catecholamines in the central nervous system;

4. Nootropic drugs;

5. Adaptogens;

1) Physiological stimulants.

Administration of small doses of catecholamines

The administration of small doses of catecholamines (strictly under medical supervision) can restore depleted reserves of catecholamines in the central nervous system and increase performance, both general and athletic.

It would be logical to assume that the introduction of catecholamines into the body will cause a response - a decrease in the synthesis of catecholamines by the body itself. This is called a negative feedback response. This is what happens, but only if catecholamines are administered in large doses. If you use small dosages, then the exact opposite situation arises: a positive feedback type reaction. In response, the body begins to produce its own catecholamines in increased quantities. To date, the most detailed method for introducing small doses of adrenaline into the body has been developed. Adrenaline is administered once a day subcutaneously in doses from 1/10 to 1/20 of the average therapeutic dose. Subcutaneous administration of adrenaline allows you to achieve a very noticeable anabolic effect and, importantly, reduces the risk of colds.

2) Introduction of catecholamine precursors into the body

All catecholamines are synthesized in the body from the amino acid phenylalanine. In general terms, the chain of catecholamine synthesis can be represented in the following way: phenylalanine -› L1-DOPA1 -› dopamine -› norepinephrine -› adrenaline.

The most physiological is to introduce the amino acid phenylalanine into the body in large quantities, on the order of several grams. This gently activates the entire sympathetic-adrenal system, increasing the content of all catecholamines in the body. Such techniques already exist, but they are still at the experimental testing stage. Treatment large doses Phenylalanine is currently being tested in a number of leading US clinics as a means to combat nervous depression.

To date, the most thoroughly developed method for introducing into the body such a precursor of catecholamines as L1-DOPA. L1-DOPA is taken orally in tablets 1 time per day, 0.5 g. L1-DOPA treatment is used in a number of Moscow clinics as a means of restoring a depleted nervous system. L1-DOPA increases post-workout release into the blood growth hormone and for this purpose it is widely used in the USA.

3) Drugs that enhance the synthesis of catecholamines in the central nervous system

There is a large class of pharmacological compounds, the so-called. antidepressants, which are used to treat nervous depression - disorders associated with low mood. In sports practice, the use of antidepressants is not common, because They do not actually have a stimulating effect. Antidepressants, however, are used in cases where it is necessary to rehabilitate an athlete, to restore him after severe exhaustion sympathetic-adrenal system. This usually happens after difficult and important competitions.

4) Nootropics .

Nootropic drugs include a whole group of drugs that are used to improve mental abilities. Distinctive feature nootropics is that they are non-toxic, capable of increasing both mental and physical performance. The mechanism of action of nootropics is based on their ability to increase the energy potential of nerve cells. The weakest link in a nerve cell is mitochondria - intracellular formations that produce energy for the cell. In evolutionary terms, these are the youngest formations, so they are extremely vulnerable and suffer from any harmful effects Firstly. But they also respond first and foremost to any positive impact. Energy supply is a key link in any exchange.

Nootropics do not affect the synthesis of catecholamines as such, but their overall energizing effect strengthens nerve cells so much that the synthesis of all neurotransmitters, including catecholamines, increases.

The most widely used nootropics in sports practice are piracetam (nootropil), sodium hydroxybutyrate (GHB), picamilon, pyriditol (encephabol). Among other things, these drugs also have a certain anabolic effect, with the exception of pyriditol. Pyriditol, however, is different from others nootropic drugs in that it is able to directly stimulate the synthesis of catecholamines in nerve cells.

Use strictly under medical supervision.

5) Adaptogens

This is a whole group of plants, non-toxic to the body, which are widely used both in medicine and in sports to stimulate performance. Adaptogens include plants such as ginseng, Eleutherococcus senticosus, Schisandra chinensis, Aralia Manchurian, Radiola rosea, high-alpha, Sterculia platanofolia, Leuzea safflower. It is noteworthy that the tonic effect of adaptogens is achieved by increasing the sensitivity of nerve cells to catecholamines. Like caffeine, adaptogens affect adenylate cyclase of cell membranes and promote the accumulation of intracellular c-AMP. This increases the sensitivity of cells to catecholamines, because c-AMP is an intracellular mediator of the neurotransmitter signal. However, unlike caffeine, even very long-term administration of adaptogens does not lead to depletion of the intracellular c-AMP pool and therefore they can be recommended for long-term use. In some countries, such as Japan, adaptogens are consumed by the entire population along with food products from infancy until death without any harmful consequences.

6) Physiological stimulants

In some cases, increased synthesis of catecholamines in the central nervous system can be achieved with physiological stimulants. Their number is very large and just listing such methods of influence would take up a lot of space. Let's consider only the most banal of them - dousing cold water.

Since ancient times, dousing with cold water has been used as a means to strengthen the nervous system and even as a means of treating many diseases. What is the mechanism of its action? Exclusively reflexive. Sharp exposure to cold causes a strong release of adrenaline and other catecholamines into the blood. In this case, the purpose of the massive release of catecholamines into the blood is to narrow the skin vessels so that the cold does not penetrate deep into the body, causing internal organs. As training develops, the release of catecholamines in response to exposure to cold becomes stronger and stronger, due to an increase in the reserve capabilities of the nervous system.

With age, the activity of catecholaminergic structures of the brain decreases, which negatively affects the endocrine balance of the body. In the central nervous system the predominance of the activity of those nerve structures, where the neurotransmitter is acetylcholine, a substance antagonistic to catecholamines.

Catecholamines and acetylcholine are, as it were, on two different sides of the same scale. The predominance of catecholamine structures suppresses acetylcholine structures and, conversely, the predominance of acetylcholine structures suppresses catecholamine structures. Nerve cells where acetylcholine serves as a neurotransmitter are, in evolutionary terms, more ancient than those where catecholamines serve as mediators, therefore they are more resistant to the aging of the body.

With age, the activity of acetylcholine structures in the brain begins to predominate. Aging of catecholamine nerve centers leads to disinhibition of acetylcholine centers. The person becomes calmer, balanced, and sedentary. Senile hand tremors are the result of the predominance of the activity of acetylcholine structures over catecholamine structures. Thinking becomes slow. Even relatively simple matters that are at a young age done jokingly, become very labor-intensive.

The trouble is that acetylcholine causes excessive activity of the adrenal cortex. This leads to increased levels of glucocorticoid hormones in the blood. Their excess has a strong negative effect and the reasons for this are as follows:

1. Glucocorticoid hormones have a strong catabolic effect. Protein breakdown increases in muscle tissue And muscle growth even as a result of the most intensive training becomes impossible. A decrease in protein synthetic processes further slows down the synthesis of catecholamines and everything starts all over again. A vicious circle arises.

2. Self-renewal of protein structures occurs most quickly in the tissues of the gastrointestinal tract, therefore the catabolic effect of glucocorticoids is primarily reflected in the stomach and intestines. Most often, ulcers of the stomach and duodenum occur. Less commonly, peptic ulcer. Knowing this mechanism, it is not difficult to guess how depletion of the nervous system leads to the development of peptic ulcer disease. Peptic ulcer, in turn, disrupts the absorption of amino acids in the intestine and reduces anabolism.

3. Protein breakdown under the influence of glucocorticoids leads to an increased level of glucose in the blood, which is formed from decayed amino acids, which leads to age-related diabetes mellitus(type II diabetes).

4. An increase in blood sugar causes a response - increased release of insulin into the blood. Insulin lowers blood sugar, causing it to be converted into fat tissue. Developing age type obesity.

5. Age-related obesity causes increased content free fatty acids in the blood. Fat breaks down into fatty acids and glycerol, which enter the blood and then return to the subcutaneous fat depots. This ensures a constant circulation of fatty acids and glycerol in the body. The greater the amount of fat under the skin, the more fatty acids in the blood; their amount in the blood is directly proportional to the amount of neutral fat in the subcutaneous depot. An age-related increase in the amount of fatty acids in the blood blocks blood T-lymphocytes, causing neutralization cellular immunity, which leads to the development of malignant tumors.

Even a superficial look at the formation of age-related pathology leads us to the idea that it can and should be treated using the entire arsenal of drugs that increase the content of catecholamines in the central nervous system. The choice of such means is currently quite wide. By using them, we can not only increase general and athletic performance, not only increase a person’s creative potential, but also actively hinder the development age-related changes, delay the aging of the body, prolong creative longevity.

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1 The sympathetic-adrenal system is a system of neurons (nerve cells) that produce catecholamines, of which there are currently dozens.

2 Sympathomimetic substances (sympathomimetics) are compounds that can stimulate nerve cells that produce catecholamines.

1 Overtraining as such is a decrease in the content of catecholamines in the central nervous system. Overtraining is a real disease, depletion of the central nervous system.

1 L1 – L1– dioxyphenylalanine.

1 "Hooe" – thinking.