ADRENALINE (Adrenalinum, lat. ad — at and renalis — renal; synonym: Epinephrinum, Suprarenin, Suprarenalin) — hormone of marrow of adrenal glands. Represents D-(—) альфа-3,4-диоксифенил-бета-метиламиноэтанол or 1-metilaminoetanolpirokatekhin, C 9 H 13 O 3 N.
Adrenaline is received from tissues of adrenal glands of cattle and pigs or a synthetic way. Represents microcrystallic powder, inodorous, bitterish on taste. Has the main character. With acids forms water soluble salts. From aqueous solutions it is besieged by ammonia and carbonates of alkali metals. Strongly reducing substance which is easily oxidized especially in alkaline condition, with formation of rose-red, yellow and brown-brown melaninopodobny products. At oxidation in certain conditions the having structure of 5,6-dihydroxy-3-oxy-N-skatole (A. M. Utevsky and V. O. Osinskaya) gives the substance (emerald-green fluorescence) which is intensively fluorescing in ultraviolet rays.
Biosynthesis of adrenaline and its turning into an organism
Adrenalin belongs to the catecholamines or pyrocatechinamines entering into group of biogenic monoamines. Source of education And. in an animal organism aromatic amino acids phenylalanine and tyrosine are. Biosynthesis And. goes through the following buffer stages: dioxyphenylalanine (DOFA), dopamine, noradrenaline (ON). Tyrosine, preformirovanny in fabric or formed of phenylalanine, turns into dioxyphenylalanine under the influence of enzyme of a tyrosinehydroxylase (necessary cofactors: the recovered pteridine, About 2 , Fe ++ ); dioxyphenylalanine is decarboxylized, being treated to action of the corresponding enzyme of the DOFA-decarboxylase (with participation of pyridoxal phosphate), and the formed dopamine turns into noradrenaline under influence dopamine - beta hydroxylases in the presence of ascorbic to - you and oxygen. The last stage of biosynthesis (transformation of noradrenaline into adrenaline) is catalyzed by enzyme feniletanolamin-N-methyltransferase (cofactors: ATP, S-adenozilmetionin). Also alternative paths of biosynthesis of Adrenaline are possible (through tyramine, oktopamin, sinefrin or through DOFA, dopamine, epinin). Main way of education And. goes through dopamine and noradrenaline — the substances playing an essential role in neuro and humoral processes. In adrenal glands (see) as hormone usually collects And. or And. and noradrenaline. There are data on separate regulation of accumulation in chromaffin fabric and secretion of these two representatives of catecholamines by it, closely connected with each other in genesis and function. The formed hormone contains in granules in a complex with ATP and protein — chromogranin. Ratio And. and ATP in granules usually 4:1. Secretion of hormone is carried out by emptying of granules in intercellular spaces, and this process has character of an exocytosis.
Active secretagogue And. acetylcholine is (marrow of adrenal glands, has a cholinergic innervation). Biosynthesis and secretion And. quickly change depending on a condition of a nervous system in its afferent, efferent and central segments. Secretion And. amplifies under the influence of emotions, a condition of tension (stress), at an anesthesia, a hypoxia, an insulin hypoglycemia, pain etc. For the first time influence of nervous irritation on secretion And. M. N. Cheboksarov showed in 1910.
The adrenaline which got to a blood channel and then to effector bodies is exposed in them to various processes of transformation (binding by various proteins, adsorption by cellular membranes and various organoids, monoaminoksidazny and quinoid oxidation, O-methylation, conjugation). The big place in exchange And. occupy consistently happening processes of O-methylation under influence catechol-au-methyltransferase (KOMT) and the oxidizing deamination catalyzed by mitochondrial monoamine oxidase with education vanililmindalny to - you as an end product. At action only catechol-au-methyltransferase an end product of exchange And. is metanefrin, and at effect of one monoamine oxidase it is formed and allocated with urine dihydroxy-mandelic to - that. Quinoid way of oxidation And. goes through degidroadrenalin (an obratimookislenny form of hormone) to digidroindolovy and indoxylic derivatives: to adrenokhry (ADH) and an adrenolyutin it (is SCARLET) which can exert a direct impact on a number of enzymatic processes, P-vitaminopodobnym action on walls of capillaries, etc. possess.
Also some metabolites which are formed on other pathways are functionally active And.
Products of exchange of hormone triple its many pharmakodinamichesky properties (pressor and hyper glycemic effects, etc.) and get new. They are not only products of an inactivation And., but also the biocatalytic factors playing an essential role in the mechanism of its action (A. M. Utevsky). And., unlike dopamine and holes of adrenaline, is exposed to quinoid oxidation easier, than monoaminoksidazny. At a thyrotoxicosis, introduction to an organism of corticosteroids deamination of hormone is activated, ways of its exchange change that can have a certain functional value.
Release of Adrenaline with urine at the person fluctuates over a wide range depending on a number of conditions [Euler, W. Raab, G. N. Kassil, V. V. Menshikov, E. Sh. Matlin, etc.]. Its most part is excreted in the form of metabolites. According to Axelrod (J. Axelrod), at a vva of a deniya to the person of soaked hormone (H3 - Adrenalinum bitartricum, intravenously on 0,3 ng/kg in min. within 30 min.) in urine it was found not changed And. 6% of the entered quantity, a free metanefrin — 5%, the connected metanefrin — 36%, vanililmindalny to - you are 41%, 3-metoksi-4-gidroksifenilglikolya — 7%, dihydroxy-mandelic to - you are 3%.
Physiological effect of adrenaline
Adrenalin is biologically highly active (laevoisomer is 12 — 15 times more active than dextrorotatory), possesses the expressed cardiotonic, pressor, hyper glycemic, kalorigenny action, causes vasoconstriction of skin, kidneys, expands coronary vessels, vessels of skeletal muscles, smooth muscles, bronchial tubes and went. - kish. a path, assisting these to redistribution of blood in an organism, oppresses motility of a uterus during the late periods of pregnancy, increases oxygen consumption, standard metabolism, a respiratory coefficient. And. influences the central and peripheral nervous system, imitating action of sympathetic nervous impulses — sympathomimetic effects (see. Noradrenalin ). Hormone influences the carrying-out system of heart and directly a myocardium, possesses positive chronotropic, inotropic and dromotropic action, a cut time be replaced by opposite effect can through a nek-swarm (build-up of pressure causes reflex excitement of the center of vagus nerves with the corresponding brake influence on heart). At animals And., entered against the background of adreno-and simpatikolitik, lowers arterial pressure. Administration of Adrenaline in an organism causes the leukocytosis caused by reduction of a spleen, increases coagulability of blood.
On Kennona (W. Cannon), adrenaline — the «emergency hormone» which is carrying out in difficult, sometimes extreme conditions, mobilization of all functions and forces of an organism for fight. Increase in excretion And. it is observed at an emotional and painful stress, overloads, a hypoxia of a different origin. Many times over allocation of Ampere-second urine increases at a pheochromocytoma.
The molecular mechanisms which are the cornerstone of the mobilizing action are revealed And. on energy resources of an organism (a glycogen, lipids). Saterlend (E. W. Sutherland) and other authors showed that under influence And. there is a transformation of ATP in cyclic 3', 5' - AMF (adenosinemonophosphate) which promotes transition of inactive b-phosphorylase in active and - the phosphorylase catalyzing disintegration (phosphorolysis) of a glycogen. The similar mechanism is found in operation And. on a lipolysis. Cyclic 3', 5' - adenosinemonophosphate can turn into usual adenosinemonophosphate under the influence of enzyme of diesterase again. These processes are quite difficult and a number of enzymes participates in them. Cyclic 3', 5' - adenosinemonophosphate is formed not only at action And., but also some other hormones, as if carrying out transfer of their action in a cell on fermental systems.
Methods of definition
For quantitative definition of Adrenaline in biological liquids and fabrics many methods were offered. The methods based on biological effect had a certain value And., however for obtaining sufficient specificity it was necessary to compare data of the researches conducted on different test objects that does such definitions very labor-consuming. The chemical methods based on receiving the painted oxidates A. or on its ability to recover some substances in colored compounds, are insufficiently specific.
The greatest distribution to a crust, time received fluorimetrichesky methods (trioksiindolovy and etilendiaminovy). Trioksiindolovy methods (Euler, V. O. Osinskaya) differ in high specificity and sensitivity.
Osinskaya's method allows along with And. and to determine by noradrenaline also products of their quinoid oxidation. There are various modifications of these methods (V. V. Menshikov, E. Sh. Matlin, A. M. Bara, P. A. Kalimang, etc.). Definition And. in urine along with definition of other catecholamines and their metabolites allows to judge a hormonal link of sympaticoadrenal system.
Drugs of adrenaline
the Most often used drugs: hydrochloride of adrenaline [Adrenalini hydrochloridum (synonym of Adrenalinum hydrochloricum)] and hydrotartrate of adrenaline [Adrenalini hydrotartras (synonym of Adrenalinum hydrotartraricum)], GFH, joint venture. B. For the outside use the hydrochloride of adrenaline is issued in the form of 0,1% of solution in bottles on 10 ml; for hypodermic, intramuscular and intravenous administration — in the ampoules containing 0,1% of solution on 1 ml. It is stored in hermetically the corked bottles of orange color or in the soldered ampoules in the place protected from light.
Hydrotartrate of adrenaline is produced in ampoules on 1 ml of 0,18% of a ramtvor for injections and in bottles on 10 ml 0,18 solutions for external use.
Indications to use. Adrenaline is good therapeutic cure for bronchial asthma since relaxes muscles of bronchial tubes; it is applied at a serum disease, a hypoglycemic coma, kollaptoidny states; it is used for a stop of bleedings of local character, especially in otorhinolaryngology and ophthalmology since causes vasoconstriction of skin and mucous membranes, to a lesser extent — vessels of skeletal muscles. Routes of administration: subcutaneously, intramusculary and outwardly (on mucous membranes), and also intravenously (a drop method).
Bibliography: Adrenaline and noradrenaline, under the editorship of N. I. Grashchenkov, M., 1964; Biogenic amines in clinic, under the editorship of V. V. Menshikov, M., 1970, bibliogr.; Manukhin B. N. Physiology of adrsno-retssitor, M., 1968, bibliogr.; Matlin E. Sh. and Menshikov V. V. Clinical biochemistry of catecholamines, M., 1967, bibliogr.; Matkovsky M. D. Pharmaceuticals, p.1, page 218, M., 1972; Utsvsky A. M. Biochemistry of adrenaline, Kharkiv, 1939, bibliogr.; Utevsky A. M. and Racine M. S. Catecholamines and corticosteroids, Usp. sovr. biol., t. 73, century 3, page 323, 1972, bibliogr.; Physiology and biochemistry of biogenic amines, under the editorship of V. V. Menshikov, M., 1969; Swede F. Pharmakodinamika of drugs from the experimental and clinical point of view, the lane with slovats., t. 1 — 2, Bratislava, 1971, bibliogr.; Mol i-noffP. Century of a. Axelrod J. Biochemistry of catecholamines, Ann. Rev. Biochem., v. 40, p. 465, 1971, bibliogr.
A. M. Utevskny.