Serotonin in serum

Reference values (norm) of serotonin concentration in the blood serum in adults - 0,22-2,05 μmol / l (40-80 mkg / l); in whole blood - 0,28-1,14 μmol / l (50-200 ng / ml).

Serotonin (oxytryptamine) is a biogenic amine, which is mainly contained in platelets. The body constantly circulates up to 10 mg of serotonin. From 80 to 95% of the total amount of serotonin in the body is synthesized and stored in enterochromaffin cells of the gastrointestinal tract. Serotonin is formed from tryptophan as a result of decarboxylation. In enterochromaffin cells of the gastrointestinal tract, most of the serotonin is adsorbed by platelets and enters the bloodstream. In large quantities, this amine is localized in several parts of the brain, it is abundant in the mast cells of the skin, it is found in many internal organs, including various endocrine glands.

Serotonin causes platelet aggregation and polymerization of fibrin molecules, with thrombocytopenia is able to normalize the retraction of the blood clot. It has a stimulating effect on the smooth muscles of blood vessels, bronchioles, intestines. Provoking an exciting effect on smooth muscles, serotonin narrows bronchioles, causes increased intestinal peristalsis, and having a vasoconstrictive effect on the vascular network of the kidneys, leads to a decrease in diuresis. Insufficiency of serotonin lies at the basis of functional intestinal obstruction. Serotonin of the brain acts depressingly on the function of the reproductive system involving the epiphysis.

The most studied way of metabolism of serotonin is its conversion into 5-hydroxyindoleacetic acid under the action of monoamine oxidase. In this way, 20-52% of serotonin is metabolized in the human body.

[1], [2], [3], [4], [5], [6]

Diseases and conditions in which the concentration of serotonin in the blood serum changes

Serotonin elevated

• Metastases of abdominal carcinoma
• Medullary thyroid cancer
• Dumping syndrome
• Acute intestinal obstruction
• Cystic Fibrosis
• Myocardial infarction

Carcinoid syndrome is a rare disease caused by increased secretion of serotonin by carcinoid, which in more than 95% of cases is located in the digestive tract (vermiform appendage - 45.9%, ileum - 27.9%, rectum - 16.7%), but can be in the lungs, the bladder, etc. Carcinoid develops from argyrophilic cells of intestinal crypts. Along with serotonin, the carcinoid produces histamine, bradykinin and other amines, as well as prostaglandins. All carcinoids are potentially malignant. The risk of malignancy increases as the size of the tumor increases.

The concentration of serotonin in the blood with carcinoid syndrome rises by 5-10 times. In healthy people, only 1% of tryptophan is used for the synthesis of serotonin, while in carcinoid patients it is used up to 60%. Increased synthesis of serotonin in a tumor leads to a decrease in the synthesis of nicotinic acid and the development of symptoms specific for the avitaminosis of PP (pellagra). In the urine of patients with malignant carcinoid, a large number of products of the metabolism of serotonin - 5-hydroxyindoleacetic and 5-hydroxyindolylaceturoic acids - are detected. Isolation of 5-hydroxyindoleacetic acid in the urine, exceeding 785 μmol / day (norm - 10,5-36,6 μmol / day), is considered a prognostically unfavorable sign. After a radical surgical removal of the carcinoid, the concentration of serotonin in the blood and the excretion of the products of its metabolism in the urine are normalized. The lack of normalization of the excretion of metabolic products of serotonin indicates a non-surgical operation or the presence of metastases. Some increase in the concentration of serotonin in the blood can be in other diseases of the digestive tract.

Serotonin is lowered

• Down Syndrome
• Untreated phenylketonuria

[7], [8], [9], [10], [11], [12]

Effect of serotonin on metabolism

In shock, the serotonin content in all organs is significantly increased, the amine exchange is disturbed and the content of its metabolites is increased.

Mechanisms for increasing serotonin and histamine content in tissues

Mechanism	The factors that cause them
Degranulation of mast cells, enterochromaffine cells of the intestine; amine liberation	Low-molecular (monoamines, diamines, aromatic amines), macromolecular (poisons, toxins, antigen-antibody complex, peptone, anaphylactin) substances
Intensification of catabolism, proteolysis, autolysis	Alteration, excess of glucocorticoids, thyroid hormones, increased activity of proteolytic enzymes, hypoxia
Increased activity of bacterial tissue mitochondrial tryptophan and histidine decarboxylase	Excess of mineralocorticoids, deficiency of glucocorticoids, excess of adrenaline and norepinephrine deficiency
Reduction of mitochondrial mono- and diamino oxidase activity	Excess corticosteroids, an increase in the concentration of biogenic amines (substrate inhibition), violation of CBS, hypoxia, hypothermia
Redistribution from the depot organs	Disturbance of microcirculation in the skin, lungs, gastrointestinal tract

Serotonin affects various types of metabolism, but mainly - on bioenergetic processes, which are significantly disturbed by shock. Serotonin causes the following changes in carbohydrate metabolism: an increase in the activity of liver, myocardium and skeletal muscle phosphorylases, a decrease in glycogen content, hyperglycemia, glycolysis stimulation, gluconeogenesis, and glucose oxidation in the pentose phosphate cycle.

Serotonin helps to increase the oxygen tension in the blood and its consumption by tissues. Depending on the concentration, it either depresses respiration and oxidative phosphorylation in the mitochondria of the heart and brain, or stimulates them. Significant (2-20 times) increase in serotonin content in tissues leads to a decrease in the intensity of oxidative processes. In a number of organs (kidneys and liver), the bioenergetic processes in which are most disturbed in shock, the serotonin content is increased especially significantly (by 16-24 times). The serotonin content in the brain is increased to a lesser extent (2-4 times) and the energy processes in it remain at a high level for a long time. The effect of serotonin on the activity of individual parts of the respiratory chain system in shock varies in different organs. If in the brain it increases the activity of NADH2 and reduces the activity of succinate dehydrogenase (SDH), then in the liver it increases the activity of SDH and cytochrome oxidase. The mechanism of enzyme activation is explained by the effect of serotonin on adenylate cyclase followed by the formation of cAMP from ATP. It is believed that cAMP is an intracellular mediator of the action of serotonin. The serotonin content in tissues correlates with the level of activity of energy enzymes (especially with SDG and ATP-ase of the liver). Activation of SDH by serotonin in shock is compensatory. However, excessive accumulation of serotonin leads to the fact that the nature of this connection becomes inverse, while the activity of SDH decreases. Limiting the use of succinic acid as an oxidation product significantly impairs the energy potential of the kidneys in shock. As the shock develops, there is a correlation between the amount of serotonin in the kidneys and the activity of LDH, which indicates the switching of the activating effect of serotonin from the use of succinate (under physiological conditions) to the consumption of lactate due to inhibition of SDG, which is an adaptive response.

In addition, serotonin affects the content and exchange of purine nucleotides, the increase in which in the mitochondria stimulates the rate of ATP turnover. Serotonin forms an reversibly dissociating micellar complex with ATP. Reduction of serotonin content in cells correlates with a decrease in the level of ATP in them.

The accumulation of serotonin in shock is to a certain extent related to a change in the content of ATP. Other types of connection of intracellular serotonin with proteins, lipids, polysaccharides and divalent cations are also possible, the level of which in tissues is also affected by shock.

The involvement of serotonin in intracellular energy processes is not only in the formation of energy, but also in the release of it with the participation of ATP hydrolases. Serotonin activates Mg-ATPase. An increase in the activity of ATPase of liver mitochondria in shock may also result from elevated serotonin levels.

Thus, the accumulation of serotonin in the body tissues in shock can actively influence the carbohydrate metabolism in glycolytic and pentose cycles, respiration and its associated phosphorylation, cumulation and the use of energy in cells. The molecular mechanism of action of serotonin is mediated by the movement of ions through the membrane.

[13], [14], [15], [16], [17], [18], [19], [20], [21]

Effect of serotonin on organ function

The effect of serotonin at the systemic level lies in its specific effect on the functional state of many organs. Intraventricular injection of serotonin in doses close to shock, and intravenous injection of b-oxytryptophan (easily penetrating the blood-brain barrier and converting into the brain into serotonin) causes phase changes in the bioelectrical activity of the brain, characteristic of the activation reaction in the cortex, hypothalamus and mesencephalic reticular formation . Similar changes in the brain are established in the dynamics of the development of shock, which indirectly indicates the significant role of serotonin in the change in CNS function in shock. Serotonin is involved in the onset of membrane potential and the organization of synaptic transmission of nerve impulses. Adaptation of the organism to extreme effects is accompanied by an increase in the serotonin content in the brain due to an increase in the power of serotonergic neurons. The increase in serotonin content in the hypothalamus activates neurosecretion and enhances the function of the pituitary gland. However, a significant accumulation of serotonin in the brain can play an important role in the development of its edema.

The multifaceted action of serotonin on the cardiovascular system is significantly expressed. Large doses (10 mg or more) cause cardiac arrest in different types of experimental animals. The direct effect of serotonin on the myocardium causes systemic and coronary hypertension, as well as severe circulatory disturbances in the cardiac muscle, accompanied by necrosis ("serotonin" infarction). At the same time, changes in the oxidative and carbohydrate-phosphorus metabolism of the myocardium are close to those that occur in disorders of the coronary circulation. On ECG with shock, there are very significant changes: rapidity with subsequent heart rate slowdown, extrasystole, gradual shift of the electrical axis of the heart to the left and deformation of the ventricular complex, which can be the result of disorders of the coronary circulation.

The effect of serotonin on blood pressure depends both on the rate, dose and method of its administration, and on the type of experimental animals. Thus, in cats, rabbits and rats, intravenous administration of serotonin causes hypotension in most cases. In humans and dogs, it initiates phase changes: short hypotension, followed by hypertension and subsequent hypotension. The carotid artery is highly sensitive even to small doses of serotonin. It is assumed that there are two types of receptors through which the pressor and depressor effect of serotonin is mediated by the parasympathetic nervous system and the carotid glomerulus. Intravenous injection of serotonin in a dose approximately corresponding to its content in the volume of circulating blood in shock, causes a decrease in systemic blood pressure, IOC and OPS. Reducing the amount of serotonin in the intestinal wall and lung tissue is probably due to the mobilization of this amine from the depot. The action of serotonin on the respiratory system can be carried out both locally and reflexively, while in rats arises bronchiolospasm and increased respiration.

The kidneys contain a small amount of serotonin, but its metabolism significantly changes with their ischemia. Large doses of serotonin cause persistent pathological vasospasm, ischemia, foci of necrosis in the cortical layer, desolation, degeneration and necrosis of the tubular apparatus. A similar morphological pattern resembles a microscopic change in the kidneys during shock. Significant (10-20 times) and persistent increase in serotonin levels in renal tissue in case of shock can cause a prolonged spasm of their vessels. A particularly high level of serotonin is observed during the period of dysuric disorders. In acute renal failure, the concentration of serotonin in the blood is increased in the oliguria and anuria stage, begins to decrease during the restoration of diuresis and normalizes to the phase of polyuria, and when recovered it falls below physiological values. Serotonin reduces renal plasma flow, the rate of glomerular filtration, diuresis, the release of sodium and chloride in the urine. The mechanism of these disorders is caused by a decrease in intramural hydrostatic pressure and filtration, as well as an increase in the osmotic gradient of sodium content in the brain substance and distal sections of the tubules, which leads to an increase in reabsorption. Serotonin is important in the mechanism of renal failure in shock.

Thus, the moderate accumulation of serotonin in the brain and its central effect in shock can be useful, especially in terms of GGAS activation. Activation of serotonin energy enzymes should also be regarded as a positive, compensatory phenomenon in shock. However, the excessively high accumulation of serotonin in the myocardium and kidneys creates the possibility of direct excess amine influence on coronary and renal circulation, disturbances in its metabolism and the occurrence of cardiac and renal insufficiency.

[22], [23], [24], [25], [26], [27]