CATECHOLAMINES (ustar. synonym: pyrocatechinamines, feniletilamina) — physiologically active agents relating to biogenic monoamines; systems are mediators (noradrenaline, dopamine) and hormones (adrenaline, noradrenaline) sympathoadrenal, or adrenergic. Sympathoadrenal system (see), humoral agents a cut are To. — an important link of adaptatsionnoprisposobitelny mechanisms; it consists of nervous department (the central and peripheral nervous system) and hormonal — marrow of adrenal glands and other accumulations of chromaffin cells.
High fiziol, the following has activity To.: adrenaline (see), noradrenaline (see) and dopamine. To. are synthesized by animal and nek-ry vegetable organisms; they contain in some vegetables and fruit (bananas, oranges).
The general orientation of influence To. consists in mobilization of systems of an organism for ensuring its vigorous activity at stressful situations. Through To. regulation of the general and local fiziol, the reactions directed to preservation of a homeostasis of an organism and its adaptation to the changing conditions of surrounding and internal environment is carried out (see. Homeostasis ). Disturbance of exchange To. or their inadequate secretion can be one of pathogenetic mechanisms in development of some diseases.
In 1895 — 1896 Oliver, Schaefer (G. Oliver, E. A. Schafer) and N. Cybulski established that the extract of marrow of an adrenal gland entered into blood to an animal raises at it the ABP. Further the substance having it effect was identified as hormone of marrow of an adrenal gland — adrenaline. O. Levi (1921) and U. By Kennon (1927) it was established that at irritation of sympathetic nerves of different bodies adrenalinopodobny substances are emitted. U. Euler and it sotr. (40 — the 50th are 20 century) identified this substance as a mediator of a sympathetic nervous system — noradrenaline. At last, in 50 — the 60th 20 century existence of dofaminergichesky neurons was established and the mediator role of dopamine is proved for them.
Dopamine (3 oxytyramine, or 1-3,4-dioksifeniletilamin) — a mediator of sympathoadrenal system, one of transmitters of excitement in synapses of c. N of page, in particular in basal gangliya; the chemical predecessor of noradrenaline and adrenaline in a chain of their synthesis. Dopamine contains in chromaffin cells of tissues of the highest animals and the person: his adrenal glands contain about 2% of all To., in nervous tissue — apprx. 50%, in lungs, a liver, intestines — more than 95%; dopamine contains also in a carotid body, in dofaminergichesky neurons of c. N of the page passing in black substance in legs of a brain and in a hypothalamus. Content of dopamine in brain fabric is stable, the period of its half-decay apprx. the 2nd hour. The greatest number of dopamine and high concentration of enzymes of its synthesis and an inactivation are found in kernels of a striate body, basal gangliya, black substance, in a kernel having a tail, a pale sphere.
Dopamine is synthesized from dioxyphenylalanine (see). Formation of dopamine is catalyzed by the piridoksalzavisimy enzyme having rather wide specificity — the decarboxylase of aromatic L-amino acids (KF 220.127.116.11) localized in cytoplasm of neuron or chromaffin cells of an adrenal gland. Reaction is competitively inhibited by alpha and methylderivatives of dioxyphenylalanine (DOFA) and tyrosine. Synthesis of dopamine and its secretion are regulated by short and long ways of a post-and presynaptic feed-back; an important role is played by activity of the return neyronalny capture of dopamine, sekretirovanny in a synaptic gap. Synthesis and secretion of dopamine are not influenced by specific blockers of capture of noradrenaline; this process can be blocked by Phenaminum, anticholinergic and antihistaminic drugs, nek-ry substances applied to treatment of parkinsonism. Metabolic transformations of dopamine differ from metabolism of noradrenaline a little and happen under the influence of the same enzymes; the main metabolites of dopamine are 3-metoksitiramin, dihydroxy-phenyl-acetic to - that, gomovanilinovy to - that, conjugates of dopamine and its metabolites with sulfuric and glucuronic to-tami. Just as dioxyphenylalanine, dopamine forms N-atsetil-and 6-oxyderivative, slowing down synthesis To., and also condensates with the aldehydes influencing dofaminergichesky receptors. Activation leads dopamine receptors in a striate body to increase in content in tissue of a brain of dofaminchuvstvitelny adenylatecyclase.
Dopamine receptors are available in mesenteric, renal, coronal vessels and vessels of the basis of a brain. Femoral arteries, vessels of skin and skeletal muscles are not sensitive to dopamine. Activity dopamine receptors strengthen Apomorphinum, tetragidropapaverolin (condensate of dopamine with own aldehyde), and blocks — a haloperidol.
Dopamine in higher concentration is weaker, than others To., activates alpha and beta and adrenergic receptors: in small concentration activates only beta1-adrenoceptors, in averages — alfa1-and beta1-adrenoceptors, and in big concentration only alfa1-adrenoceptors. Activating alfa2-adrenergic receptors of chromaffin cells and presynaptic neurons, dopamine participates in regulation of secretion
K. Dofamin increases cordial emission, causes vasodilatation of kidneys with strengthening of a renal blood-groove, increase in glomerular filtering, a diuresis, excretion with urine of potassium and sodium, improves a blood stream in mesenteric and coronal vessels, but is capable to have also vasopressor effect. Stimulating a glycogenolysis and suppressing utilization of glucose in fabrics, dopamine increases concentration of glucose in blood. It stimulates formation of somatotropic hormone and causes increase in its concentration in blood, but slows down secretion of prolactin. Insufficiency of synthesis of dopamine in striopallidal system causes disturbances of motive function — a syndrome parkinsonism (see), hyperkinesias (see). Sharp increase in excretion of dopamine and its metabolites with urine is observed at hormonal and active tumors of a sympathetic nervous system (sympathoblastomas), and also at introduction healthy and sick the drug L-DOFA. At avitaminosis of B6 (e.g., at hron, alcoholism) the content of dopamine in a brain increases, there are its metabolites possessing patol, action and aggravating disease.
Methods of definition of dopamine in fabrics and biol, liquids same, as well as methods of definition of others To. (see below).
The dopamine entered into an organism from the outside badly gets through a blood-brain barrier therefore in the therapeutic purposes enter L-DOFA, from to-rogo dopamine is formed (see. Dioksifenilalanin as drug ). At introduction direct dependence between concentration of dopamine in blood and fiziol, activity of drug is established to people and animals of the drug L-DOFA.
Catecholamines in an organism
To. also placentae are found in the highest animals and the person at all stages of ontogenesis in all fabrics, except bone; they are closely connected with an adrenergic innervation of bodies. In experiments it is shown that surgical, immunol, or the chemical desimpatization leads to falloff of contents To. in fabrics, and the subsequent regeneration of sympathetic nerves leads to recovery of their normal contents. Stimulation of sympathetic nerves electric current causes allocation of noradrenaline. 3H-noradrenaline entered into blood actively is taken the different fabrics having a sympathetic innervation and then allocated at stimulation of sympathetic nerves.
The greatest number To. is synthesized and collects in marrow adrenal glands (see); in other bodies of mammals, except for c. N of page, the basic To. noradrenaline is. In the course of ontogenesis concentration To. and abundance of adrenaline increase in adrenal glands. So, at laboratory animal (rats) concentration of noradrenaline from the first to the 120th day after the birth increases in adrenal glands more than by 20 times, and adrenaline — more than by 40 times.
In c. N of page of the person and the highest animals To. are distributed unevenly. The greatest number of noradrenaline is revealed in a hypothalamus and a myelencephalon, dopamine — in basal gangliya and black substance. Possibility of education and accumulation of adrenaline in c. the N of page in fiziol, conditions is discussed.
The main regulatory influences of sympathoadrenal system are carried out through marrow of adrenal glands and noradrenergichesky neurons; along with them in c. N of page exist regulatory dofaminergichesky neurons, they are found in a striate body, limbic system, a retina of an eye and some other educations.
For quantitative assessment funkts, conditions of sympathoadrenal (adrenergic) system at the person can be used data on maintenance To. in blood and urine (tab. 1).
Biosynthesis and inactivation of catecholamines
In 1939 Mr. of H. Blaschko suggested about the sequence of stages of synthesis To. in an organism that was completely confirmed later. The main predecessor To. the amino acid circulating in blood tyrosine is, edges gets into sympathetic neurons and marrow of an adrenal gland where enzymatic synthesis is carried out To. on the next main way: tyrosine — dioxyphenylalanine — dopamine — noradrenaline — adrenaline (scheme 1).
Nek-roye quantity tyrosine (see) it can be formed of phenylalanine. However such way of formation of tyrosine (an auxiliary way), apparently, has no essential value since with food tyrosine in the quantities sufficient for biosynthesis gets to an organism To. and for other requirements of an organism. Therefore it is considered that the first stage of synthesis To. the hydroxylation of tyrosine in dioxyphenylalanine which is carried out by enzyme a tyrosinehydroxylase (KF 18.104.22.168) is. This enzyme is in cytoplasm of neuron or chromaffin cells, possesses high substrate and stereospecificity. The tetrapteridinovy cofactor, ions of bivalent iron and oxygen is necessary for its activity. This stage of synthesis To. — the limiting stage, its speed defines intensity of all process. As inhibitors tyrosine hydroxylase serve alpha methyl-p-tyrosine, 3 iodtyrosine, parachlorphenylalanine, etc. By the principle of a negative feed-back DOFA, dopamine, noradrenaline, adrenaline and their metabolites can act as inhibitors. The second stage — decarboxylation of dioxyphenylalanine — leads to formation of the first mediator of adrenergic system of dopamine; in dofaminergichesky neurons on it synthesis stops.
Formation of noradrenaline from dopamine is catalyzed dopamine - a beta hydroxylase (KF 22.214.171.124) — cupriferous enzyme, for activity to-rogo it is required ascorbic to - that. At this stage synthesis of a mediator in noradrenergichesky neurons and hormone in noradrenalinovy cells of adrenal glands comes to the end.
Dopamine - the beta hydroxylase catalyzes a hydroxylation not only dopamine, but also other derivatives of a feniletilamin. This enzyme is localized in reserve katekholaminovy granules (vesicles) of adrenergic neurons and chromaffin cells of adrenal glands. The most known inhibitor of enzyme is Teturamum, or Antabusum.
The last stage of synthesis To. methylation of noradrenaline under the influence of enzyme of fenilaminoetanol-N-methyltransferase with participation of S-adenozilmetionina as donator of methyl groups is. This process happens in cytoplasm where there is granules noradrenaline. Formation of adrenaline from noradrenaline at mammals goes only in chromaffin cells. At amphibians adrenaline is formed also in adrenergic neurons where it serves as a mediator.
To. collect in special organellas of a cell — reserve granules (vesicles) where they are in the connected form. To. make 6,7% of weight of reserve granules, water — 68,5%, proteins-chromogranins — 11,5%, lipids — 7%, adeninenucleotides — 5,1%, Tsitokhroma — 0,3%. Are in reserve granules also dopamine - a beta hydroxylase, ions of sodium, potassium, magnesium and zinc. At nervous impulse of a vesicle approach a synaptic membrane and allocate a mediator in a synaptic gap. The exocytosis is considered the most probable mechanism of allocation: granules are built in a presynaptic membrane of neuron, their cover reveals, and contents get to a synaptic gap. At the same time together with To. in a synaptic gap chromogranins and dopamine - a beta hydroxylase which are found in blood are emitted. Considerable part K. (60 — 90%), allocated at nervous impulse, it is taken in adrenergic neuron again and gets to reserve granules. Process of capture goes with the participation of Na + — K + - dependent ATP-ase (KF 126.96.36.199). Capture To. in neurons it is blocked by cocaine, an imipramine, and in reserve granules — Reserpinum.
Inactivation To. it is reached them by consecutive O-methylation and deamination. To. can be inactivated under the influence of generally two enzymes: monoamine oxidase (KF 188.8.131.52) and catechol-au-methyltransferase (KF 2.1.1. 6). These enzymes take part also in processes of a catabolism To. On the scheme 2 ways of an inactivation are presented To. with participation of the specified enzymes on the example of noradrenaline and adrenaline.
Formed under influence monoaminoxidases (see) products of oxidizing deamination To. lose the specific activity, but gain new properties; apparently, they participate in regulation of exchange of glucose in muscles, heart, a brain, a liver, etc. Catechol - About - metiltransferaza transfers methyl group from S-adenozilmetionina to phenolic group K. in meta-situation, forming metoksiproizvodny of K. Pochti in all cases this enzyme is localized in cytoplasm; as a rule, the most part of enzyme is out of adrenergic neurons. Products of O-methylation To. — weak sympathomimetics, but active inhibitors of ekstraneyronalny binding To. Products of oxidizing deamination and O-methylation To. are removed from an organism kidneys, both their content and structure in urine allow to judge about funkts, a condition of mediator and hormonal links of adrenergic system at a stress, pathology and physical. to loading.
Biological activity of catecholamines
Biological activity of catecholamines is shown in their property to influence on funkts, a condition of bodies and intensity of metabolic processes in fabrics. To. excite in a varying degree activity of c. N of page, speed up and strengthen reductions of heart, increase or reduce the peripheric resistance of blood vessels, cause relaxation of unstriated muscles of intestines and bronchial tubes, stimulate a glycogenolysis and a lipolysis, strengthen protein metabolism, influence movement of ions of sodium, potassium, calcium through cellular membranes, etc.
Separate To., providing in general similar reactions of an organism, differ on the nature of influence on different bodies. So, noradrenaline causes narrowing practically of all departments of a vascular bed whereas adrenaline can lead to vasodilatation of skeletal muscles and decrease in the general peripheric resistance. Effect of dopamine on cardiovascular system is similar to noradrenaline, but is expressed to a lesser extent whereas its peripheral vascular effects are closer to effect of adrenaline. Noradrenaline, unlike adrenaline, can slow down heart rate, perhaps, due to reflex excitement of a vagus nerve in response to increase in the ABP. Apparently, the mechanism of staging biol, effects of drugs K is same. at their introduction to the person and animals.
In animal experiments it was established that biol, effects To. considerably depend on a dose and a way of introduction. So, high doses of dopamine cause increase in the ABP, and small — decrease. Small doses of noradrenaline brake sokratitelny ability of unstriated muscles of the isolated vas deferens of a Guinea pig, and high doses — strengthen. Effect of adrenaline and noradrenaline on an isolated heart is qualitatively identical though quantitatively noradrenaline works more weakly.
Biol, activity To. it is caused by their property to communicate and influence adrenoreaktivny systems of cells (see. Adrenoreaktivnaya system ), t. e, on adrenoceptors which are considered as a macromolecule (perhaps, metalloproteins) with a certain three-dimensional configuration, additional in relation to molecules K. Affinity different To. to certain adrenoceptors is explained by compliance of their structures funkts, groups. So, biol, activity of noradrenaline is caused by existence of the ionized amino groups and phenolic hydroxyl in meta-situation, and also an alcoholic hydroxyl, capable to enter low-energy communication with the anion and cationic centers, and also with forming hydrogen bindings funkts, groups of adrenoceptors. Degree of affinity To, to p-adrenoceptors depends by nature the radical at a nitrogen atom, on spirit and phenolic hydroxylic groups. To manifestation biol, activities To. it is possible to prevent by introduction adrenolytic means (see), i.e. by blockade of adrenoceptors.
Similarity of effects To. it is caused by common features of their structure that allows each of To. to react with any kind of adrenoceptors. Distinctions in character biol, activities separate To. are defined by different degree of their affinity (various size of a constant of linkng) with separate types of adrenoceptors. Allocate four types of adrenoceptors according to the nature of effects of agonists, i.e. To. both their analogs (adrenomimetik), and antagonists, i.e. adrenoblockers (adrenolytic drugs). Alpha Adrenoceptors in the greatest measure react to an alpha adrenomimetik noradrenaline; beta adrenoceptors — on beta-adrenergic agonist izopropilnoradrenalin (a synthetic analog To.). Adrenaline almost equally influences both types of receptors. Beta receptors are divided into the subgroups which are differently reacting to stimulation their sambutamoly and braking by Practololum and butoksaminy. Dopamine is most active concerning specific dofaminergichesky receptors, conceding at action on alpha receptors to noradrenaline and adrenaline, and on beta receptors as well an izopropilnoradrenalina.
The effects gained at excitement of adrenoceptors of different bodies are not identical (tab. 2).
Apparently, excitement To. specific adrenoceptors on sympathetic nerve termination slows down allocation To. neuron that plays an important role in the termination of transfer of nervous impulse on an effector cell. In other words, biol, activity To. is the cornerstone of the mechanism of self-control of the sympathetic nervous device. In a complete organism biol, activity To. effects of other systems interacting with K. Tak cannot separately be considered from biol, To. take part in regulation of release by a hypothalamus of rileasing-factors (liberin), AKTG and somatotropic hormone — a hypophysis, insulin — beta cells of insular tissue of pancreas, a renin (KF 184.108.40.206) — juxtaglomerular cells of kidneys.
In turn, biologically active agents of other systems exert the expressed impact on manifestations biol, activities K. Tak, corticosteroids (see) exponentiate action To. on c. N of page, cardiovascular system, thyroxine (see) influences metabolism To., insulin (see) is an antagonist of action To. on carbohydrate and a lipometabolism.
Biol, activity To. significantly changes in the course of their metabolism. So, O-methylation of noradrenaline leads to weakening of its influence on beta adrenoceptors of a myocardium approximately by 1000 times, however does not change its influence on alpha adrenoceptors of a blink membrane. Products of oxidizing deamination of adrenaline — aldehydes are capable to stimulate oxidation of glucose whereas adrenaline has no this effect.
The proteins of adrenoceptors which are localized in a cellular membrane, apparently, perform function of selection, perception, transformation and strengthening of the signal arriving to a cell in the form of a molecule K. The subsequent links of the mechanism of action To. are presented by system of enzymes: the adenylatecyclase (KF 220.127.116.11) and phosphodiesterase (KF 18.104.22.168) participating in implementation biol, activities of many hormones.
The general catalytic activity of adenylatecyclase depends on the factors defining physical. - a chemical condition of a cellular membrane (ATP, calcium ions). In animal experiments it is established that noradrenaline increases activity of specific gormonochuvstvitelny adenylatecyclase and brakes (in high concentration) activity of phosphodiesterase. Long introduction of noradrenaline exerts the return impact on both enzymes.
Adenylatecyclase catalyzes education from ATP cyclic adenylic to - you (3', 5 '-adenosinemonophosphorus to - you), carrying out in a cell a role of a mediator of excitement by activation of a protein kinase (KF 22.214.171.124), and also, perhaps, at the expense of a translocation of intracellular calcium.
Substrates of the phosphorylation dependent from cyclic 3', 5 '-AMF, serve the kinase of phosphorylase (KF 126.96.36.199) catalyzing reaction of modification of a glikogenfosforilaza (KF 188.8.131.52), an uridindifosfatglyukoza-glycogen — the glucosyltransferase (KF 184.108.40.206) and a gormonochuvstvitelny lipase (KF 220.127.116.11) operating directly on a glycogen and triglycerides, causing mobilization of glucose and not esterified fat to - t, and also troponin. Modification of a molecule of a troponin under the influence of a kinase of phosphorylase and phosphatase of phosphorylase (KF 18.104.22.168), apparently, changes regulation actin-miozinovogo of influence and is responsible for a positive inotropic effect To. This process demands ions of Ca 2+ in concentration about 1 µmol. Transfer of ions of Ca 2+ through a membrane it is important for actions To. on interface of excitement and reduction of a muscle. According to Byulbring (E. Bulbring, 1973), excitement of beta adrenoceptors stimulates absorption of ions of Ca 2+ , and excitement of alpha adrenoceptors — release of ions of Ca 2+ in unstriated muscles. Biol, effect stops upon transition cyclic 3', 5 '-AMF in 5' - AMF and dephosphorylation of proteins. In implementation by a cell biol, activities To. also allosteric mechanisms (in relation to regulation of activity of muscular or heart phosphorylase), complexes of the enzymes regulating the speed of reactions with the macromolecular complexes containing their substrates (a glycogen, triglycerides) can participate.
Catecholamines at morbid conditions
Insufficiency To. in an organism does not develop even during removal of both adrenal glands since extraadrenal chromaffin fabric and sympathetic nerve terminations fill adrenomedullary function. Bystry increase in secretion To. usually occurs as nonspecific reaction of adaptation of an organism to change of external or internal living conditions.
Adrenaline — «hormone of alarm» and noradrenaline as a mediator of nervous functions participate in formation of the general adaptation syndrome (see), since the very first stage of influence of the exciting agent. They activate gipotalamo - pituitary and adrenal system, provide metabolic and hemodynamic adaptive reactions. Participation of sympathoadrenal system in reactions of an organism to stressful influences is shown by increase in excretion with urine K. and their metabolites (at emotional, physical. to loading, surgery, in the period of an exacerbation of diseases of internals etc.). At excessive loading (extreme states) after phases of bystry excitement and steady activation of sympathoadrenal system there comes its exhaustion. At long stress (see) increase in activity of enzymes of synthesis is established To. and decrease of the activity of enzymes of their metabolism. At people at the same time ratios of content in urine K are broken., their metabolites and predecessors.
Inadequate hyper - or the gipokatekholaminemiya caused by disturbance of synthesis, secretion, an inactivation or removal To., and also change of sensitivity of adrenoceptors of fabrics is led to disturbance of regulation of functions of bodies and systems, to patol, to reactions and diseases.
A cut hyper synthesis and hypersecretion To happen an example of pathology, at. with relative insufficiency of their inactivation, the hormonal and active tumor of chromaffin fabric is — pheochromocytoma (see). Despite inclusion at a pheochromocytoma in action of various ways of an inactivation To. and protective decrease in sensitivity of fabric adrenoceptors, fiziol, action To. gets patol, a form that the wedge, pictures of a disease leads to development typical: attacks of arterial hypertension, tachycardia, arrhythmia of heart, dystrophy of a myocardium, to a hyperphrenia, tremor of fingers of hands, perspiration, and also strengthening of a glycogenolysis and lipolysis, etc. For a pheochromocytoma patognomonichno sharp increase in content in urine K. and their metabolites.
Hyper synthesis To. at a tumor of nervous tissue — a sympathoblastoma (see. Neuroblastoma ) is followed by an adequate hypermetabolism To. in fabric of a tumor. Klien, a picture, in addition to symptoms of a tumor, is caused by the increased content of dopamine in blood — a giperdofaminemiya; content in urine K. and especially their metabolites (gomovanilinovy and vanililmindalny to - t) it is sharply raised.
Disturbance of synthesis of dopamine in black substance of a brain leads to development of motive frustration — to parkinsonism (see). At the same time the content of dopamine and its metabolite — gomovanilinovy to - you not only in fabrics of c is reduced. N of page, but also in cerebrospinal liquid and in urine. Activity of enzymes of synthesis To. — DOFA-decarboxylases and dopamine - beta hydroxylases in basal gangliya it is also reduced. The most low level of excretion of dopamine with urine accompanies postentsefalichesky parkinsonism. It is possible that in a pathogeny of parkinsonism a part is played by disturbance of metabolism of dioxyphenylalanine, and not just dopamine.
Genetically caused disturbances of activity of enzymes of metabolism To. can lead to development migraines (see). Excess accumulation in a brain of a metabolite of dopamine — the tetragidropapaverolin at hron, alcoholism is connected with accustoming to alcohol. The family dizautonomiya is followed by low activity dopamine hydroxylase at reduced activity of a sympathetic nervous system.
The genetic nature of schizophrenia, and also a mediator role To. the central structures regulating emotional and behavioural reactions forced to assume that in a pathogeny of this disease normal or unusual metabolites can play a part To. At schizophrenia (see) increase in activity catechol-au-methyltransferase of erythrocytes by 1,5 times in comparison with norm and decrease of the activity of monoamine oxidase in thrombocytes is noted; the tendency to decrease of the activity of monoamine oxidase in thrombocytes is connected with genetic predisposition to schizophrenia. At schizophrenia increase in excretion vanililmindalny to - you with urine is revealed. The possibility of toxic action patol, products of exchange is shown To. on tissue of a brain, and in urine of patients with schizophrenia it is found 3,4-dimetiloksifeniletilamin (patol. product of double O-methylation of dopamine). Connection between types of disturbance of exchange is established To. and the nature of affective manifestations at schizophrenia and maniac-depressive psychosis. At the same time most of researchers found increase in allocation with urine of noradrenaline or adrenaline (or both amines at the same time), and in a depressive stage — relative (in comparison with a maniacal stage) or absolute (it is lower than the level of norm) decrease in their excretion. Excretion with urine of noradrenaline in a maniacal phase is highest maniac-depressive psychosis (see), but the maniacal syndrome at schizophrenia, a psychopathia and vascular disorders is not followed by increase in excretion of noradrenaline.
Activity of enzymes of an inactivation To. also changes: monoamine oxidase in thrombocytes at patients with maniac-depressive psychosis is moderately reduced and raised at patients with depressions. Activity catechol-au-methyltransferase in erythrocytes at a depression is reduced. Activity of enzyme of synthesis To. dopamine - beta hydroxylases it is not changed neither at schizophrenia, nor at maniac-depressive psychosis.
Studying of content in urine and cerebrospinal liquid 3-metoksi-4-oksifenilglikolya (one of the main metabolites of noradrenaline in c. N of page) allowed to differentiate different types of depressions (at hron, the maintenance of this metabolite is higher than a characterologic depression, than at maniac-depressive psychosis) and to define the choice of therapy.
Especially significant increase in excretion To. observe at delirium tremens in the period of a maximum of development of symptoms, and reduction of excretion To. and contents of adrenaline in blood it is revealed at an oligophrenia. Sharp increase in allocation is characteristic of epilepsy To. with urine in the period of an attack and decrease during the mezhpristupny period.
Various nevrol, diseases are also followed by disturbances of exchange To., most likely secondary order. At patients myasthenia (see) excretion with urine of noradrenaline it is a little raised, and adrenaline — it is reduced, however at long disease removal and noradrenaline decreases. At myopathies (see) relative insufficiency of an adrenal link of sympathoadrenal system — decrease in excretion of adrenaline, change of force and an orientation of reactions of this system on funkts, tests is found (cold, with introduction of AKTG). At patients with various forms of a striatal syndrome with hyperkinesias adrenaline and dopamine are removed with urine in the increased quantities. In cerebrospinal liquid low contents gomovanilinovy to - you is revealed at an amyotrophic lateral sclerosis and a multiple sclerosis.
The expressed pain syndrome at neuralgia is followed by activation of sympathetic and adrenal departments of sympathoadrenal system. During the period preceding an attack of migraine, excretion with urine of adrenaline decreases. At a craniocereberal injury excretion with urine and the content in blood K. raise in proportion to weight of an injury.
Ideas of a pathogeny of some diseases of cardiovascular system connect with a role emotional stress (see), including with funkts, disorders of exchange To. At the same time increase in removal with urine K is established. and their metabolites during the spontaneous and provoked hypertensive crises, and also in a prestage and the I stage of an idiopathic hypertensia (on G. F. Lang and A. L. Myasnikov's classification, in a neurotic stage of a disease — on classification of E. M. Tareeva). Excretion To. with urine in the I stage of an idiopathic hypertensia does not differ quantitatively from that at a hypertensive form of vegeto-vascular dystonia, and the III stage — does not differ from fiziol. norms. According to some authors, at experimental arterial hypertension it is found that activity of enzyme of synthesis To. dopamine - beta hydroxylases raises in proportion to degree of hypertensia, however at the long course of a disease activity of this enzyme decreases below, than at control group of animals. At animals with genetically caused hypertensia increase in activity of enzymes of an inactivation is revealed To. in erythrocytes and walls of vessels.
Exchange of catecholamines at various hemodynamic options of a current of the III (sclerous) stage of an idiopathic hypertensia (on E. To M. Tareev) it is broken differently:
at patients with dominance of increase in cordial emission more adrenaline, dopamine and gomovanilinovy to - you is removed with urine, than patients with dominance have increases in peripheric resistance. Similarity between hemodynamic effects of the dopamine entered in an experiment and a condition of a hemodynamics at patients with the III (sclerous) stage of an idiopathic hypertensia at preferential increase in cordial emission is noted. At various stages of an idiopathic hypertensia increase in excretion of dopamine and its ratio distortion with noradrenaline towards dominance of dopamine is shown. At patients with an idiopathic hypertensia the day-night rhythm of excretion is broken To., what reflects, perhaps, disturbances of the central regulation of processes of their exchange. By means of different loadings it is established that at an idiopathic hypertensia reactivity of vessels in response to action To. it is raised. Antihypertensives normalize reaction of vessels on To., though indicators of excretion To. at the same time can not change.
At symptomatic (renal) arterial hypertension excretion To. it is raised since a renin-angiotenzinnaya the system activates their secretion. However at disturbances of azotovydelitelny function of kidneys clearance To. sharply falls, and their excretion with urine decreases.
Development of atherosclerosis of vessels is followed by decrease in level of removal with urine K. At a combination of atherosclerosis to coronary heart disease in the period of attacks of stenocardia and in initial stages of a myocardial infarction activation of all sympathoadrenal system with increase in contents is observed To. in blood, in a myocardium, and also with increase in contents To. and their metabolites in urine. The possibility of metabolic (dystrophic) not coronary damage of a myocardium at hyper activation of sympathoadrenal system is known, however clinically and biochemical it is not differentiated from a koronarogenny heart attack. Increase or decrease in excretion To. at different diseases — see table 1.
On different stages of exchange To. as in c. N of page, and influence peripheries drugs of hypotensive, antidepressive and sedative action. Adreno-and sympatholytics, activators and blockers of adrenoceptors are applied at arterial hypertension, coronary insufficiency, arrhythmias of heart, bronchial asthma, at some mental diseases, during the carrying out a neyroleptanalgeziya. The important place in rehabilitation of patients with a myocardial infarction is taken by the antidepressants and sedative drugs influencing exchange To selected individually. in c. N of page.
Drugs of catecholamines are used preferential for stopping of attacks of bronchial asthma, allergic rhinitis, at a collapse, at overdose of insulin and other states — see. Adrenaline, drugs ; Dioksifenilalanin, drugs ; Noradrenalin, drugs .
Methods of definition
Because content in blood K. quickly changes, and also because of methodical difficulties of definition of concentration To. in blood secretory activity of sympathoadrenal system in a wedge, conditions was defined usually by identification of excretion with urine free To. and their predecessor — DOFA, and also metabolites To. — vanililmindalny and gomovanilinovy to - t. For assessment of processes of exchange To. determine the size of activity of enzymes of synthesis and metabolism To. in blood, uniform elements of blood and fabrics.
Methods of definition To. find application in diagnosis of tumors chromaffin (pheochromocytoma) and sympathetic nervous fabrics (a sympathoblastoma, a neuroblastoma, a ganglioneuroma), in differential diagnosis of arterial hypertension, at profound studying of neurohumoral regulation for patients with mental diseases with affective frustration (schizophrenia, maniac-depressive psychosis), at control of effect of hypotensive, antidepressive drugs, various ways of anesthesia, during the studying of pathogenetic mechanisms of the diseases which are followed by vascular frustration, allergic manifestations, a pain syndrome.
Definition of catecholamines in biological liquids. Biol, the methods based on definition of influence To. on a tone of unstriated muscles of different bodies or on the ABP level of an animal, are applied a little.
Colorimetric methods (see. Colorimetry ) are based or on measurement of coloring of oxidates K., or colourings arsenomolibdenovy to - you, recovered by adrenaline in certain conditions. Pretreatment by alkali of solution of adrenaline considerably increases intensity of coloring, unlike solution of noradrenaline and substances, other, close on a structure. The colorimetric method is insufficiently specific as have ability to recover arsenomolibdenovy to - that, in addition to To., many substances, napr, phthiocol, pyrocatechin, etc. B. N. Manukhin (1964) offered the option of a colorimetric method differing in the preliminary differentiated oxidation of adrenaline and noradrenaline magnesium oxide at various pH values in the corresponding adrenokhroma. At the subsequent addition the chamois to - you forms leykooksoadrenokhroma which it is better, than initial To., recover arsenomolibdenovy to - that. With the known reservations colorimetric methods find application at funkts, the tests, for registration happening at the same time changes though the absolute value of contents To. in blood they do not allow to establish.
Most flyuorimetrichesky methods of definition were widely adopted (see. Flyuorimetriya ). The first option of these methods — trioksiindolovy — is based on transformation of adrenaline and noradrenaline into fluorescent products — adrenolyutin and noradrenolyutin. The second option is based on formation of fluorescent condensation products K. with ethylene diamine. In the USSR as the unified method of definition To. since the beginning of the 70th of 20 century the trioksiindolovy method in V. V. Menshikov's modifications (definition of free adrenaline and noradrenaline in urine, 1961), E. Sh. Matlina, etc. is accepted (definition of adrenaline, noradrenaline, dopamine and DO FA in one portion of urine, 1965). These methods are applied to determination of content To. and in fabrics. Also V. O. Osinskaya's method (1957) for definition is used To. in fabrics, in A. M. modification Bara (1962) — for determination of content To. in urine. At a wedge, use of these methods it must be kept in mind a possibility of an interference of a number of medicinal substances: quinidine, polycyclic antibiotics, alfa-metil-DOFA.
By means of gas chromatography (see) and mass spectrometry (see) perhaps separate definition To., sensitivity till 10-16 asking, at high specificity and an opportunity to carry out up to 50 tests a day.
The increasing value gets studying of predecessors and metabolites To., and also the enzymes participating in a catalysis of synthetic reactions and K. Metoksilirovannye's metabolism metabolites of adrenaline and noradrenaline metanefrin and normetanefrin, and also vanililmindalny to - that (a product of methylation and oxidizing deamination) are defined in urine by a colorimetric or flyuorimetrichesky way after their preliminary separation from other phenolic connections with the help of various options of a chromatography or electrophoresis (see).
Histochemical methods of definition in fabrics K. and some other biogenic amines (serotonin) are specific and have high sensitivity. These methods are widely used in normal and patol, morphology for studying of an adrenergic innervation of bodies and distribution of biogenic amines in nerve centers. In a basis gistokhy, methods ability of monoamines to form with formaldehyde of connection (flyuorofor) possessing active lies luminescence (see). Chemical reaction of formation of flyuorofor proceeds in two stages: 1) condensation of a side chain of monoamines with formaldehyde in a cycle (Pictet's reaction — Spengler); 2) dehydrogenation of a cycle with formation of the luminescing products. To. at this stage form 3-4-degidrokhinoliny, and serotonin — 3-4 - degidro - beta karboliny.
Two options of a method of identification of biogenic amines are standard.
At one option it is used paraforms (so-called gaseous formaldehyde); other option is based on use of water solutions of formaldehyde. Use the paraform yields good results. Pieces of fabric are quickly taken, frozen, subjected to freeze drying, then processed paraformy at high temperature and a certain humidity within 1 — 3 hour. This method was simplified afterwards: drying of fabric was replaced with dehumidification of freshly cooked cryostately cuts in the exsiccator over phosphorus pentoxide that reduced duration of freeze drying and even completely excluded it. The second option of a method is based on ability of monoamines to form the luminescing connections during the processing of fabrics water solution of formaldehyde — the so-called water method of identification of monoamines which is in detail developed by A. V. Sakharova and D. A. Sakharov (1968). For prevention of diffusion of monoamines cold solutions of formaldehyde are used (t ° 0 — 4 °). Concentration of formaldehyde can vary from 1 to 10%. It is possible to process pieces of fabric and cryostately cuts; dry up them on air or in a drying oven at t ° 40 — 60 ° within 1 — 3 hour. At the same time for acceleration of reaction cuts warm up during three — five minutes at t ° 100 °. Then cuts are concluded in not luminescing immersion oil and investigated in a luminescent microscope. Catecholamines possess a green luminescence, and serotonin gives a yellow luminescence.
The quantitative flyuorimetriya of monoamines in fabrics is complicated because at their high concentration linear relation between the content of monoamines and intensity of their luminescence («effect of clearing») is broken. Therefore semi-quantitative methods are widely applied. They consist in a visual estimate of intensity of a luminescence and in calculation of number of the shining structures. At small concentration of monoamines it is possible to apply successfully a flyuorimetriya and photometry (see), having a little altered at the same time processing of material. V. A. Grantyn and V. S. Chesnin (1972) simplified A. V. Sakharova and D. A. Sakharov's method; they mounted cryostately cuts on cover glasses and processed 10% the solution of formalin prepared on Ringer's solution — Locke (pH — 7,4). Then cuts dried in the exsiccator over phosphoric anhydride within 45 min. at t ° 40 °, concluded in not luminescing immersion oil and investigated in a luminescent microscope of ML-4 with the subsequent photographing in reference conditions. Films fotometrirovat on a microphotometer of MF-2 with measurement of intensity of a background and the shining cells.
Table 1. The MAINTENANCE of CATECHOLAMINES AT the PERSON is NORMAL ALSO AT PATHOLOGY
Table 2. ADRENERGIC EFFECTS IN SOME BODIES, SYSTEMS AND TYPES of EXCHANGE [according to E. J. Ariens et al., 1964]
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B. H. Manukhin, V. V. Menshikov, T. D. Bolshakova; T. B. Zhuravleva (stalemate. An.).