Adrenal medulla hormones, catecholamines. Catecholamines and their action

Some human hormones and connections endocrine system With nervous system are presented in Fig. 13.2. Under direct control of the nervous system are the adrenal medulla and the hypothalamus; other endocrine glands are associated with the nervous system indirectly, through the hormones of the hypothalamus and pituitary gland. The cells of the hypothalamus synthesize special peptides - liberins (releasing hormones). In response to stimulation of certain brain centers, liberins are released from axons nerve cells hypothalamus, ending in the pituitary gland, and stimulate the synthesis and release of tropic hormones by pituitary cells. Along with liberins, the hypothalamus produces statins, which inhibit the synthesis and secretion of pituitary hormones.

Central nervous system

Nervous relations

Nerve connections ___
	Hypothalamus		Antidiure-
			tic
			Oxytocyp		muscles of the uterus,
					mammary glands
			Melanocyte-
			stimulate-		Melanocytes
			stimulating hormone
			Prolactia		Mammary glands
Somatotropin
			Lutsinizi-		Folliculo-
	Corticotropin	Thyrotropin		stimulating
Brain		Thyroid			Testes
substance
	adrenal glands
adrenal glands
ADRENALIN	CORTISOL	THYROXINE ESTROGENS			ANDROGENS

Rice. 13.2. Connections between the endocrine and nervous systems. Solid arrows indicate the synthesis and secretion of the hormone, dotted arrows indicate the effect of the hormone on target organs

Classification of hormones by biological functions to a certain extent conditional, since many hormones are multifunctional. For example, adrenaline and norepinephrine regulate not only the metabolism of carbohydrates and fats, but also heart rate, smooth muscle contraction, blood pressure. In particular, for this reason, many hormones, especially paracrine ones, cannot be classified according to their biological functions.

Changes in hormone concentrations in the blood

The concentration of hormones in the blood is low, on the order of IO6-IO JJ mol/l. Half-life in the blood is measured in minutes, for some hormones - tens of minutes, less often - hours. An increase in the concentration of a hormone in the blood under the action of a corresponding stimulus depends on an increase in the rate of synthesis of the hormone or the rate of secretion of the hormone already present in the blood. endocrine cell hormone.

Steroid hormones are lipophilic substances that easily penetrate through cell membranes. Therefore, they do not accumulate in cells, and an increase in their concentration in the blood is determined by an increase in the rate of synthesis.

Peptide hormones are released into the blood with the participation of special secretion mechanisms. These hormones, after their synthesis, are included in secretory granules - membrane vesicles formed in the lamellar complex; the wasp hormone is released into the blood by fusion of granules with plasma membrane cells (exocytosis). Hormone synthesis occurs quickly (for example, a proinsulin molecule is synthesized in 1-2 minutes), while the formation and maturation of secretory granules require more time - 1-2 hours. The storage of the hormone in secretory granules ensures a rapid response of the body to the stimulus. : the stimulus accelerates the fusion of granules with the membrane and the release of stored hormone into the blood.

Synthesis of steroid hormones

The structure and synthesis of many hormones are described in previous sections. Steroid hormones are a group of compounds related in origin and structure: they are all formed from cholesterol. Intermediate products during synthesis steroid hormones Pregnenolone and progesterone serve (Fig. 13.3). They are formed in all organs that synthesize any steroid hormones. Further, the transformation paths diverge: in the adrenal cortex, cortisol (glucocorticosteroid) and aldosterone (mineralocorticosteroid) (C,-steroids) are formed, in the testes - male sex hormones (C19-steroids), in the ovaries, female sex hormones (C18-steroids) . Most of the arrows in the diagram hide not one, but two to four reactions. In addition, alternative pathways for the synthesis of some hormones are possible. In general, the pathways for the synthesis of steroid hormones form a rather complex network of reactions. Many intermediates of these pathways also have some hormonal activity. However, the main steroid hormones are cortisol (regulation of carbohydrate and amino acid metabolism), aldosterone (regulation water-salt metabolism), testosterone, estradiol and progesterone (regulation of reproductive functions).

As a result of inactivation and catabolism of steroid hormones, a significant amount of steroids containing a keto group at position 17 (17-ketosteroids) is formed. These substances are excreted through the kidneys. Daily excretion of 17-ketosteroids in adult woman is 5-15 mg, in men - 10-25 mg. The determination of 17-ketosteroids in urine is used for diagnosis: their excretion increases in diseases accompanied by overproduction of steroid hormones, and decreases in underproduction.

Progesterone (C21) Aldosterone (C21)

Rice. 13.3. Pathways for the synthesis of steroid hormones:

1,2 - in the adrenal cortex, testes and ovaries; 3, 4 - in the adrenal cortex; 5 - in the testes and ovaries; 6 - in the ovaries

Paracrine hormones

Cytokines

Cytokines are signaling molecules with paracrine and autocrine actions; they practically never exist in the blood in physiologically active concentrations (with the exception of interleukin-1). Dozens of different cytokines are known. These include interleukins (lymphokines and monokines), interferons, peptide growth factors, and colony-stimulating factors. Cytokines are glycoproteins containing 100-200 amino acid residues. Most cytokines are produced and act in many types of cells and respond to various stimuli, including mechanical damage, viral infection, metabolic disorders etc. The exception is interleukins (IL-1a and IL-1R) - their synthesis is regulated by specific signals and in a small number of cell types.

Cytokines act on cells through specific membrane receptors and protein kinase cascades, as a result, transcription factors are activated - enhancers or silencers, proteins that are transported into the cell nucleus, find a specific DNA sequence in the promoter of the gene that is the target of this cytokine, and activate or suppress gene transcription .

Cytokines are involved in the regulation of proliferation, differentiation, chemotaxis, secretion, apoptosis, inflammatory reaction. Transforming growth factor (TGF-β) stimulates the synthesis and secretion of extracellular matrix components, cell growth and proliferation, and the synthesis of other cytokines.

Cytokines have overlapping, but still different biological activities. Cells different types, or varying degrees differentiation, or being in different functional state may respond differently to the same cytokine.

Eicosanoids

Arachidonic acid, or eicosatetraenoic acid, 20:4 (5, 8, 11, 14), gives rise to a large group of paracrine hormones - eicosanoids. Arachidonic acid, which comes from food or is formed from linoleic acid, is included in the composition of membrane phospholipids and can be released from them as a result of the action of phospholipase A. Next, eicosanoids are formed in the cytosol (Fig. 13.4). There are three groups of eicosanoids: prostaglandins (PG), thromboxanes (TX), leukotrienes (LT). Eicosanoids are formed in very small quantities and, as a rule, have short time life - measured in minutes or even seconds.

Leukotrienes

Rice. 13.4. Synthesis and structure of some eicosanoids:

1 - phospholipase A2; 2 - cyclooxygenase

in different tissues and different situations different eicosanoids are formed. The functions of eicosanoids are diverse. They cause contraction of smooth muscles and constriction of blood vessels (PGF2Ct, synthesized in almost all organs) or, conversely, relaxation of smooth muscles and dilation of blood vessels (PGE2, also synthesized in most organs). PGI2 is synthesized mainly in the vascular endothelium, inhibits platelet aggregation, and dilates blood vessels. Thromboxane TXA2 is synthesized mainly in platelets and also acts on platelets - it stimulates their aggregation (autocrine mechanism) in the area of ​​vascular damage (see Chapter 21). Thromboxane TXA2 also constricts blood vessels and bronchi, acting on smooth muscle cells (paracrine mechanism).

Eicosanoids act on target cells through specific membrane receptors. The connection of the eicosanoid with the receptor turns on the mechanism of formation of the second (intracellular) signal messenger; they can be cAMP, cGMP, inositol trisphosphate, Ca2+ ions. Eicosanoids, along with other factors (histamine, interleukin-1, thrombin, etc.), are involved in the development of the inflammatory response.

Inflammation is a natural response to tissue damage, initial link healing. However, sometimes inflammation is excessive or too prolonged, and then it itself becomes a pathological process, a disease, and requires treatment. To treat such conditions, inhibitors of eicosanoid synthesis are used. Cortisol and its synthetic analogues (dexamethasone, etc.) induce the synthesis of lipocortin proteins, which inhibit phospholipase A2 (see Fig. 13.4). Aspirin (a non-steroidal anti-inflammatory drug) acetylates and inactivates cyclooxygenase (Fig. 13.6).

Rice. 13.6. Inactivation of cyclooxygenase by aspirin

Catecholamine hormones - dopamine, norepinephrine and adrenaline - are 3,4-dihydroxy derivatives of phenylethylamine. They are synthesized in chromaffin cells of the adrenal medulla. These cells got their name because they contain granules that turn red-brown when exposed to potassium bichromate. Clusters of such cells were also found in the heart, liver, kidneys, gonads, adrenergic neurons of the postganglionic sympathetic system and in the central nervous system.

The main product of the adrenal medulla is adrenaline. This compound accounts for approximately 80% of all medulla catecholamines. Outside medulla adrenaline is not produced. In contrast, norepinephrine, found in organs innervated by sympathetic nerves, is formed predominantly in situ (~80% of the total); the rest of norepinephrine is also formed mainly in nerve endings and reaches its targets in the blood.

The conversion of tyrosine to epinephrine involves four sequential steps: 1) ring hydroxylation, 2) decarboxylation, 3) side chain hydroxylation, and 4) N-methylation. The pathway of catecholamine biosynthesis and the enzymes involved in it are presented in Fig. 49.1 and 49.2.

Tyrosine - hydroxylase hydroxylase

Tyrosine is the immediate precursor of catecholamines, and tyrosine hydroxylase limits the rate of the entire process of catecholamine biosynthesis. This enzyme is found both in free form and in a form bound to subcellular particles. With tetrahydropteridine as a cofactor, it performs an oxidoreductase function, converting L-tyrosine to L-dihydroxyphenylalanine (-DOPA). There are different ways to regulate tyrosine hydroxylase as a rate-limiting enzyme. The most important of these is inhibition by catecholamines according to the principle feedback: catecholamines compete with the enzyme for the pteridine cofactor, forming a Schiff base with the latter. Tyrosine hydroxylase, in addition, is competitively inhibited by a number of tyrosine derivatives, including α-methyltyrosine. In some cases, this compound is used to block excess production of catecholamines in pheochromocytoma, however, there are more effective drugs that also have less pronounced side effect. Compounds of another group suppress the activity of tyrosine hydroxylase by forming complexes with iron and thus removing the existing cofactor. An example of such a compound is a,-dipyridyl.

Catecholamines do not cross the blood-brain barrier and, therefore, their presence in the brain must be explained by local synthesis. In some diseases of the central nervous system, such as Parkinson's disease, there are disturbances in the synthesis of dopamine in the brain. Precursor to dopamine

Rice. 49.1. Biosynthesis of catecholamines. ONMT-phenylethanolamine-N-methyltransferase. (Modified and reproduced, with permission, from Goldfien A. The adrenal medulla. In: Basic and Clinical Endocrinology, 2nd ed. Greenspan FS, Forsham PH. Appleton and Lange, 1986.)

FA easily crosses the blood-brain barrier and therefore serves as an effective treatment for Parkinson's disease.

DOPA decarboxylase

Unlike tyrosine hydroxylase. Found only in tissues capable of synthesizing catecholamines, DOPA decarboxylase is present in all tissues. This soluble enzyme requires pyridoxal phosphate to convert -DOPa to -dihydroxyphenylethylamine (dopamine). The reaction is competitively inhibited by compounds that resemble α-DOPA, such as α-methyl-DOPA. Halogenated compounds form a Schiff base with -DOPA and also inhibit the decarboxylation reaction.

α-Methyl-DOPA and other related compounds, such as α-hydroxytyramine (derived from tyramine), α-methylyrosine, and metaraminol, have been used successfully to treat some forms of hypertension. The antihypertensive effect of these metabolites is apparently due to their ability to stimulate α-adrenergic receptors (see below) of the corticobulbar system in the central nervous system, which leads to a decrease in the activity of peripheral sympathetic nerves and lowering blood pressure.

Dopamine b-hydroxylase

Dopamine b-hydroxylase (DBH) is a co-oxidase mixed function, catalyzing the conversion of dopamine to norepinephrine. DBG uses ascorbate as an electron donor and fumarate as a modulator; The active site of the enzyme contains copper. DBG of adrenal medulla cells is probably localized in secretory granules. Thus, the conversion of dopamine to norepinephrine occurs in these organelles. DBG is released from adrenal medulla cells and nerve endings together with norepinephrine, but (unlike the latter) is not reuptaken by nerve endings.

Phenylethanolamine-N-methyltransferase

The soluble enzyme phenylethanolamine - -methyltransferase (PCMT) catalyzes the -methylation of norepinephrine to produce adrenaline in adrenaline-producing cells of the adrenal medulla. Since this enzyme is soluble, it can be assumed that the conversion of norepinephrine to adrenaline occurs in the cytoplasm. The synthesis of TYMT is stimulated by glucocorticoid hormones that penetrate into the medulla through the intraadrenal portal system. This system provides 100 times greater concentration of steroids in the medulla than in the systemic arterial blood. Such a high concentration in the adrenal glands is apparently necessary for the induction

Catecholamines are physiologically active substances that can be presented both as mediators and hormones. They are very important in the control and molecular interactions between cells in humans and animals. Catecholamines are produced by synthesis in the adrenal glands, more precisely, in their medulla.

All higher human activities associated with the functioning and activity of nerve cells are carried out with the help of these substances, since neurons use them as intermediaries (neurotransmitters) transmitting nerve impulses. Not only physical, but also mental endurance depends on catecholamine metabolism in the body. For example, not only the speed of thinking, but also its quality depends on the quality of the metabolic processes of these substances.

A person’s mood, the speed and quality of memorization, the reaction of aggression, emotions and the general energy tone of the body depend on how actively catecholamine is synthesized and used in the body. Catecholamines also trigger oxidation and reduction processes in the body (carbohydrates, proteins and fats), which release the energy necessary to nourish nerve cells.

Enough large quantities catecholamines are present in children. That is why they are more mobile, emotionally rich and learnable. However, with age, their number decreases significantly, which is associated with a decrease in the synthesis of catecholamines both in the central nervous system and in the peripheral. This is associated with a slowdown in thought processes, memory deterioration and decreased mood.

Now catecholamines include four substances, three of which are brain neurotransmitters. The first substance is a hormone, but not a transmitter, and is called serotonin. Contained in platelets. The synthesis and storage of this substance occurs in cellular structures gastrointestinal tract. It is from there that it is transported into the blood and further, under its control, the synthesis of biologically active substances occurs.

If its levels in the blood are increased by 5–10 times, then this may indicate the formation of tumors of the lungs, intestines or stomach. At the same time, in a urine test, the indicators of serotonin breakdown products will be significantly increased. After surgical intervention and the tumor is eliminated, these indicators in the blood plasma and urine return to normal. Their further study helps to exclude possible relapse or the formation of metastases.

Less possible reasons increase in the concentration of serotonin in the blood and urine – acute heart attack myocardium, thyroid cancer, acute intestinal obstruction etc. A decrease in serotonin concentration is also possible, which indicates Down syndrome, leukemia, hypovitaminosis B6, etc.

Dopamine is the second hormone from the catecholamine group. A brain neurotransmitter synthesized in special brain neurons that are responsible for regulating its basic functions. It stimulates the ejection of blood from the heart, improves blood flow, dilates blood vessels, etc. With the help of dopamine, the glucose level in a person’s blood increases due to the fact that it prevents its utilization, while simultaneously stimulating the process of glycogen breakdown.

The regulatory function in the formation of human growth hormone is also important. If an increased level of dopamine is observed during a urine test, this may indicate the presence of a hormonally active tumor in the body. If the indicators are lowered, then the motor function body (Parkinson's syndrome).

No less important hormone, is norepinephrine. In the human body it is also a neurotransmitter. It is synthesized by the cells of the adrenal glands, the endings of the synoptic nervous system and the cells of the central nervous system from dopamine. Its amount in the blood increases in a state of stress, great physical. stress, bleeding and other situations requiring immediate response and adaptation to new conditions.

He has vasoconstrictor effect and mainly affects the intensity (speed, volume) of blood flow. Very often this hormone is associated with rage, since when it is released into the blood, an aggressive reaction occurs and muscle strength increases. The face of an aggressive person turns red precisely due to the release of norepinephrine.

Adrenaline is a very important neurotransmitter in the body. The main hormone contained in the adrenal glands (their medulla) and synthesized there from norepinephrine.

Associated with the reaction of fear, since with a sharp fright its concentration increases sharply. As a result, the frequency increases heart rate, increases blood pressure, coronary blood flow increases, glucose concentration increases.

Also causes vasoconstriction of the skin, mucous membranes and organs abdominal cavity. In this case, the person’s face may become noticeably pale. Adrenaline increases the endurance of a person in a state of excitement or fear. This substance is an important doping for the body and therefore, the greater its amount in the adrenal glands, the more active the person is physically and mentally.

Study of catecholamine levels

Currently, the result of catecholamine testing is important indicator the presence of tumors or other serious diseases of the body. To study the concentration of catecholamines in the human body, two main methods are used:

1. Catecholamines in blood plasma. This method research is the least popular, since the removal of these hormones from the blood occurs instantly, and an accurate study is only possible when it is taken at the moment acute complications(for example, hypertensive crisis). As a result, it is extremely difficult to carry out such research in practice.
2. Urinalysis for catecholamines. In a urine test, hormones 2, 3 and 4 are examined in our list presented earlier. As a rule, daily urine is examined, and not a one-time sample, since during one day a person may be exposed to stressful situations, fatigue, heat, cold, physical activity. stress, etc., which provokes the release of hormones and helps to obtain more detailed information. The study includes not only determining the level of catecholamines, but also their metabolites, which significantly increases the accuracy of the results. You should take this study seriously and exclude all factors that distort the results (caffeine, adrenaline, physical activity and stress, ethanol, nicotine, various medicines, chocolate, bananas, dairy products).

The data of the research results can be influenced by many external factors. Therefore, in combination with analyses, physical and emotional state the patient, what medications he takes and what he eats. When undesirable factors are eliminated, the study is repeated to ensure accurate diagnosis.

Although tests for the concentration of catecholamines in the human body can help in detecting a tumor, they are, unfortunately, unable to show the exact location of its origin and its nature (benign or malignant). They also do not show the number of tumors formed.

Catecholamines are essential substances for our body. Thanks to their presence, we can cope with stress, physical overload, and increase our physical, mental and emotional activity. Their indicators will always warn us about dangerous tumors or diseases. In response, you just need to pay enough attention to them and promptly and responsibly examine their concentration in the body.

The effects of catecholamines begin with interaction with specific receptors on target cells. If the receptors for thyroid and steroid hormones are localized inside cells, then the receptors for catecholamines (as well as acetylcholine and peptide hormones) are present on the outer cell surface.

It has long been established that in relation to some reactions, epinephrine or norepinephrine are more effective than the synthetic catecholamine isoproterenol, while in relation to others, the effect of isoproterenol is superior to that of adrenaline or norepinephrine. On this basis, the concept was developed that there are two types of adrenergic receptors in tissues: a and B, and in some of them only one of these two types can be present.

Isoproterenol is the most potent beta-adrenergic agonist, while the synthetic compound phenylephrine is the most potent a-adrenergic agonist. Natural catecholamines - adrenaline and norepinephrine - are able to interact with both types of receptors, but adrenaline shows a greater affinity for beta-receptors, and norepinephrine - for a-receptors. Catecholamines activate cardiac β-adrenergic receptors more strongly than smooth muscle β-receptors, which made it possible to divide the β-type into subtypes: β1-receptors (heart, fat cells) and β2 receptors (bronchi, blood vessels etc.). The effect of isoproterenol on β1 receptors is only 10 times greater than the effect of adrenaline and norepinephrine, while on β2 receptors it acts 100-1000 times stronger than natural catecholamines.

The use of specific antagonists (phentolamine and phenoxybenzamine for α- and propranolol for β-receptors) confirmed the adequacy of the classification of adrenergic receptors. Dopamine is able to interact with both α- and β-receptors, but in various tissues (brain, pituitary gland, blood vessels) their own dopaminergic receptors are also found, the specific blocker of which is haloperidol. The number of β-receptors ranges from 1000 to 2000 per cell.

The biological effects of catecholamines, mediated by β-receptors, are usually associated with activation of adenylate cyclase and an increase in intracellular cAMP content. The receptor and the enzyme, although functionally connected, are different macromolecules. Guanosine triphosphate (GTP) and other purine nucleotides take part in the modulation of adenylate cyclase activity under the influence of the hormone receptor complex. By increasing the activity of the enzyme, they apparently reduce the affinity of β-receptors for agonists.

The phenomenon of increased sensitivity of denervated structures has long been known. On the contrary, prolonged exposure to agonists reduces the sensitivity of target tissues. The study of β-receptors made it possible to explain these phenomena.

It has been shown that long-term exposure to isoproterenol leads to a loss of sensitivity of adenylate cyclase due to a decrease in the number of β-receptors. The process of desensitization does not require activation of protein synthesis and is probably due to the gradual formation of irreversible hormone-receptor complexes. On the contrary, the administration of 6-oxidopamine, which destroys sympathetic endings, is accompanied by an increase in the number of responsive β-receptors in tissues. It is possible that an increase in sympathetic nervous activity also causes age-related desensitization of blood vessels and adipose tissue in relation to catecholamines.

The number of adrenergic receptors in different organs can be controlled by other hormones. Thus, estradiol increases, and progesterone decreases, the number of α-adrenergic receptors in the uterus, which is accompanied by a corresponding increase and decrease in its contractile response to catecholamines. If the intracellular “second messenger” formed under the action of β-receptor agonists is most likely cAMP, then with regard to the transmitter of α-adrenergic influences the situation is more complicated. Assumed to exist various mechanisms: decrease in cAMP level, increase in cAMP content, modulation of cellular calcium dynamics, etc.

To reproduce the various effects in the body, doses of adrenaline are usually required that are 5-10 times smaller than norepinephrine. Although the latter is more effective against α- and β1-adrenergic receptors, it is important to remember that both endogenous catecholamines are capable of interacting with both α- and β-receptors. Therefore the biological reaction of this body on adrenergic activation largely depends on the type of receptors present in it. However, this does not mean that selective activation of the nervous or humoral part of the sympathetic-adrenal system is impossible. In most cases, there is increased activity of its various parts. Thus, it is generally accepted that hypoglycemia reflexively activates the adrenal medulla, while a decrease in blood pressure (postural hypotension) is accompanied mainly by the release of norepinephrine from the endings of the sympathetic nerves.

In table 24 shows selected data characterizing the type of adrenergic receptors in various tissues and the biological reactions mediated by them.

Table 24. Adrenergic receptors and the effects of their activation in various tissues

It is important to consider that the results intravenous administration catecholamines do not always adequately reflect the effects of endogenous compounds. This applies mainly to norepinephrine, since in the body it is released mainly not into the blood, but directly into synaptic clefts. Therefore, endogenous norepinephrine activates, for example, not only vascular α-receptors (increased blood pressure), but also cardiac β-receptors (increased heart rate), while the introduction of norepinephrine from the outside leads mainly to the activation of vascular α-receptors and reflex (through the vagus) slowing heartbeats.

Low doses of adrenaline activate mainly β-receptors of muscle vessels and the heart, resulting in a decrease in peripheral vascular resistance and an increase in cardiac output. In some cases, the first effect may predominate, and hypotension develops after the administration of adrenaline. In more high doses Adrenaline also activates α-receptors, which is accompanied by an increase in peripheral vascular resistance and, against the background of an increase in cardiac output, leads to an increase in blood pressure.

However, its effect on vascular β-receptors also remains. As a result, the increase in systolic pressure exceeds that of diastolic pressure (increase pulse pressure). When introducing large dosesα-mimetic effects of adrenaline begin to predominate: systolic and diastolic pressure increase in parallel, as under the influence of norepinephrine.

The effect of catecholamines on metabolism consists of their direct and indirect effects. The former are realized mainly through β-receptors. More complex processes associated with the liver. Although increased hepatic glycogenolysis is traditionally considered to be the result of activation of β-receptors, there is also evidence of the participation of α-receptors in this.

The indirect effects of catecholamines are associated with modulation of the secretion of many other hormones, such as insulin. The action of adrenaline on its secretion is clearly dominated by the α-adrenergic component, since it has been shown that any stress is accompanied by inhibition of insulin secretion. The combination of direct and indirect effects of catecholamines causes hyperglycemia, associated not only with an increase in hepatic glucose production, but also with inhibition of its utilization peripheral tissues. Accelerated lipolysis causes hyperlipacidemia with increased delivery of fatty acids to the liver and intensified production ketone bodies. Increased glycolysis in muscles leads to an increase in the release of lactate and pyruvate into the blood, which, together with glycerol released from adipose tissue, serve as precursors of hepatic gluconeogenesis.

Regulation of catecholamine secretion

The similarity of the products and methods of response of the sympathetic nervous system and the adrenal medulla was the basis for combining these structures into a single sympathetic-adrenal system of the body, distinguishing its nervous and hormonal components. Various afferent signals are concentrated in the hypothalamus and the centers of the spinal and medulla oblongata, from where efferent messages emanate, switching to the cell bodies of preganglionic neurons located in the lateral horns of the spinal cord at the level of the VIII cervical - II-III lumbar segments.

The preganglionic axons of these cells leave spinal cord and form synaptic connections with neurons localized in the ganglia of the sympathetic chain, or with cells of the adrenal medulla. These preganglionic fibers are cholinergic. The first fundamental difference between sympathetic postganglionic neurons and chromaffin cells of the adrenal medulla is that the latter transmit the cholinergic signal arriving to them not through the nerve conduction (postganglionic adrenergic nerves), but through the humoral pathway, releasing adrenergic compounds into the blood. The second difference is that postganglionic nerves produce norepinephrine, while adrenal medulla cells produce predominantly adrenaline. These two substances have different action on fabric.

Phenylethylamines or catecholamines - what are they? These are active substances that act as mediators in intercellular chemical interactions in the human body. These include: norepinephrine (norepinephrine), which are hormonal substances, as well as dopamine, which is a neurotransmitter.

General information

Catecholamines - what are they? These are several hormones that are produced in the adrenal gland, its medulla and enter the bloodstream as a response to an emotional or physical stressful situation. Further, these active substances take part in the transmission nerve impulses into the brain, provoke:

• release of energy sources, which are fatty acids and glucose;
• dilation of pupils and bronchioles.

Norepinephrine directly increases blood pressure by constricting blood vessels. Adrenaline acts as a metabolic stimulant and increases heart rate. After the hormonal substances have completed their work, they disintegrate and are excreted from the body along with urine. Thus, the functions of catecholamines are that they provoke the endocrine glands to active work, and also help stimulate the pituitary gland and hypothalamus. Normally, catecholamines and their metabolites are contained in small quantities. However, under stress, their concentration increases for some time. In some pathological conditions (chromaffin tumors, neuroendocrine tumors), a huge amount of these active substances is formed. Tests can detect them in blood and urine. In this case, the following symptoms appear:

• increased blood pressure for a short or long period;
• very severe headaches;
• trembling in the body;
• increased sweating;
• prolonged anxiety;
• nausea;
• slight tingling in the limbs.

It is considered an effective method for treating tumors surgery aimed at its removal. As a result, catecholamine levels decrease and symptoms decrease or disappear.

Mechanism of action

The effect is to activate membrane receptors located in cell tissue target organs. Further, protein molecules, changing, trigger intracellular reactions, due to which a physiological response is formed. Hormonal substances produced by the adrenal glands and thyroid gland, increase the sensitivity of receptors to norepinephrine and adrenaline.

These hormonal substances affect the following types brain activity:

• aggressiveness;
• mood;
• emotional stability;
• reproduction and assimilation of information;
• quick thinking;
• participate in shaping behavior.

In addition, catecholamines provide energy to the body. High concentration This complex of hormones in children leads to their mobility and cheerfulness. As the child grows older, the production of catecholamines decreases and the child becomes more reserved, intense mental activity decreases slightly, possibly worsening mood. By stimulating the hypothalamus and pituitary gland, catecholamines help increase activity endocrine glands. Intense physical or mental stress, in which the heart rate increases and body temperature rises, lead to an increase in catecholamines in blood flow. The complex of these active substances acts rapidly.

Types of catecholamines

Catecholamines - what are they? These are biologically active substances that, due to their instant response, allow the individual’s body to work ahead of the curve.

1. Norepinephrine. This substance has another name - the hormone of aggression or rage, since when it enters the bloodstream, it provokes irritability and increased muscle mass bodies. The amount of this substance is directly related to large physical overloads, stressful situations, or allergic reactions. Excess norepinephrine, having a constricting effect on blood vessels, has a direct effect on the speed of circulation and blood volume. The person's face takes on a red tint.
2. Adrenalin. The second name is the fear hormone. Its concentration increases with excessive worries, stress, both physical and mental, as well as with severe fear. This hormonal substance is formed from norepinephrine and dopamine. Adrenaline, by constricting blood vessels, provokes an increase in pressure and affects the rapid breakdown of carbohydrates, oxygen and fats. The individual's face takes on a pale appearance, endurance when strong excitement or fear increases.
3. Dopamine. This active substance, which is involved in the production of norepinephrine and adrenaline, is called the happiness hormone. Effects on the body vasoconstrictor effect, provokes an increase in the concentration of glucose in the blood, suppressing its utilization. Inhibits the production of prolactin and affects the synthesis of growth hormone. Dopamine affects sex drive, sleep, thought processes, joy, and pleasure from eating. An increase in the excretion of dopamine from the body along with urine is detected in the presence of tumors of a hormonal nature. In brain tissue, the level of this substance increases with a lack of pyridoxine hydrochloride.

Biological action of catecholamines

Adrenaline significantly affects cardiac activity: it increases the conductivity, excitability and contractility of the myocardial muscle. Under the influence of this substance, blood pressure increases, and also increases:

• strength and heart rate;
• minute and systolic blood volume.

Excessive concentration of adrenaline can provoke:

• arrhythmia;
• in rare cases, ventricular fibrillation;
• disruption of oxidation processes in the heart muscle;
• changes in metabolic processes in the myocardium, up to dystrophic changes.

Unlike adrenaline, norepinephrine does not have a significant effect on cardiac activity and causes a decrease in heart rate.

Both hormonal substances:

• They have a vasoconstrictor effect on the skin, lungs and spleen. In adrenaline this process is more pronounced.
• Expand coronary arteries stomach and heart, while the effect of norepinephrine on coronary arteries stronger.
• Play a role in metabolic processes body. Adrenaline has the predominant effect.
• Helps reduce muscle tone in the gallbladder, uterus, bronchi, and intestines. Norepinephrine is less active in this case.
• They cause a decrease in eosinophils and an increase in neutrophils in the blood.

In what cases is a urine test prescribed?

An analysis of catecholamines in urine makes it possible to identify disorders that, due to pathological processes, lead to disorders normal functioning body. The causes of failures can be various serious illnesses. This type of laboratory test is prescribed in the following cases:

1. To monitor therapy in the treatment of chromaffin tumors.
2. In case of neuroendocrine or identified tumor of the adrenal glands, or genetic predisposition to tumor formation.
3. For hypertension that cannot be treated.
4. Presence of hypertension with constant headache, rapid heartbeat and increased sweating.
5. Suspicion of a chromaffin neoplasm.

Preparing for a urine test

Determination of catecholamines helps to confirm the presence of pathological processes in the human body, for example, high blood pressure and oncology, as well as to ensure the effectiveness of treatment for pheochromocytoma and neuroblastoma. For accurate analysis results, you should undergo preparation, which consists of the following:

• Two weeks before the procedure, do not take medications that affect the increased release of norepinephrine from the endings of adrenergic nerves, in agreement with the treating doctor.
• Do not take medications that have a diuretic effect for two days. Exclude tea, coffee, alcohol-containing drinks, cocoa, beer, as well as cheese, avocado and other exotic vegetables and fruits, all legumes, nuts, chocolate, all products that contain vanillin.
• During the day and during the period of daily urine collection, avoid any overexertion and avoid smoking.

Immediately before collecting urine for catecholamine analysis, perform genital hygiene. Biological material is collected three times a day. The first morning portion is not taken. Three hours after this, urine is collected, the second time - after six and then, after 12 hours. Before being sent to the laboratory, the collected biomaterial is stored in a sterile container placed in a special box or refrigerator at a certain temperature. The time of the first and last emptying is indicated on the urine collection container bladder, personal data of the patient, date of birth.

for catecholamines

In the laboratory, the biomaterial is examined for several indicators, which depend on the age and gender of the individual. The unit of measurement for hormones is mcg/day; each type has its own standards:

• Adrenalin. Acceptable values ​​for citizens over 15 years of age are 0-20 units.
• Norepinephrine. Norm for age category from 10 years - 15-80.
• Dopamine. The indicator corresponds normal values 65-400 from 4 years of age.

The results of the study of catecholamines in urine are influenced by various factors. And since pathology in the form of a chromaffin tumor is quite rare, the indicators are often false positive. In order to reliably diagnose the disease, additional types of examinations are prescribed. If elevated levels of catecholamines are detected in patients with an already established diagnosis, this fact indicates a relapse of the disease and the ineffectiveness of the therapy. It should be remembered that taking certain groups of medications, stress, drinking alcohol, coffee and tea affects end result research. Pathologies in which an increased concentration of catecholamines is detected:

• liver diseases;
• hyperthyroidism;
• myocardial infarction;
• angina pectoris;
• bronchial asthma;
• peptic ulcer duodenum or stomach;
• head injury;
• long-term depression;
• arterial hypertension.

Low levels of hormonal substances in urine indicate diseases:

• kidney;
• leukemia;
• various psychoses;
• underdevelopment of the adrenal glands.

Preparing for a blood test for catecholamines

14 days before taking samples, it is necessary to exclude medications containing sympathomimetics (in consultation with the treating doctor). For two days, exclude from the diet: beer, coffee, tea, cheese, bananas. Quit smoking in a day. Refrain from eating for 12 hours.

Blood is taken through a catheter, which is installed one day before taking biomaterial samples due to the fact that puncture of the vein also increases the concentration of catecholamines in the blood.

Panel “Blood catecholamines” and serotonin + urine test for GVK, VVK, 5-OIUC

Using such a panel, the content of catecholamines is determined: serotonin, dopamine, norepinephrine, adrenaline and their metabolites. Indications for use this study the following:

• determination of causes hypertensive crises And arterial hypertension;
• for the purpose of diagnosing neoplasms nerve tissue and adrenal glands.

More information can be obtained when prescribing a daily urine analysis to determine the level of catecholamines due to the fact that their synthesis during this period is influenced by:

• pain;
• cold;
• stress;
• injuries;
• heat;
• physical stress;
• asphyxia;
• any types of loads;
• bleeding;
• use of drugs of a narcotic nature;
• lowering blood glucose levels.

With diagnosed arterial hypertension, the concentration of catecholamines in the blood approaches the highest level of normal values, and in some cases approximately doubles. IN stressful situation adrenaline in the blood plasma increases tenfold. Due to the fact that catecholamines in the blood are neutralized quite quickly, for diagnosis pathological conditions it is appropriate to detect them in urine. Practicing doctors prescribe tests for the concentration of norepinephrine and epinephrine mainly to diagnose hypertension and pheochromocytoma. In young children, in order to confirm neuroblastoma, it is important to determine the metabolites of norepinephrine and adrenaline, as well as dopamine.

In order to obtain reliable information about catecholamines, urine analysis also determines the presence of their breakdown products: HVA (homovanillic acid), VMA (vanillylmandelic acid), normetanephrine, metanephrine. The excretion of metabolic products normally exceeds the excretion of a complex of hormonal substances. The concentration of metanephrine and ICH in urine is greatly increased in pheophromocytoma, which is important for making a diagnosis.

It is a breakdown product of adrenaline and norepinephrine; it is detected in a daily analysis for catecholamines. Indications for the purpose of the analysis are neuroblastomas, tumors and assessment of the functioning of the adrenal glands, hypertension and crises. The study of this metabolite allows us to draw a conclusion about the synthesis of adrenaline and norepinephrine, and also helps in the diagnosis of neoplasms and assessment of the adrenal medulla.

Serotonin

In oncological practice, to detect a special type of tumor with argentaffin, a blood indicator such as the catecholamine serotonin is important. It is considered one of and is a highly active biogenic amine. The substance has a vasoconstrictor effect, takes part in regulating temperature, respiration, pressure, kidney filtration, stimulates smooth muscles intestines, blood vessels, bronchioles. Serotonin can cause platelet aggregation. Its content in the body is detected using the metabolite 5-OHIAA (hydroxyindoleacetic acid) of urine. The serotonin content is increased in the following cases:

• carcinoid tumor of the abdominal cavity with metastases;
• hypertensive crises with a diagnosis of pheochromocytoma;
• neuroendocrine tumors of the prostate, ovaries, intestines, bronchi;
• pheochromocytomas;
• metastasis or incomplete removal of the tumor after surgery.

In the body, serotonin is converted into hydroxyindoleacetic acid and is excreted in the urine. The concentration of this substance in the blood is determined by the amount of excreted metabolite.

Catecholamines - what are they? These are useful substances for any individual, necessary for the body’s immediate response to an irritant: stress or fear. A blood test shows the presence of hormones immediately at the time of taking the biomaterial, and a urine test shows only the previous day.