[Glutamate decarboxylase activity and GABA binding in the brain synaptic membranes in rats with compensatory activation of hypothalamo-pituitary-adrenal system in stress]. / Hlutamatdekarboksylazna aktyvnist' i zv'iazuvannia HAMK synaptychnymy membranamy mozku shchuriv za diï stresu na tli kompensatornoï aktyvatsiï hipotalamo-hipofizarno-adrenokortykal'noï systemy.

The reaction of the rat adrenal cortex and medulla to stress was absent under conditions of compensatory activations of function of hypothalamic-pituitary-adrenal system. At the same time, glutamate decarboxylase activity was increased in the hypothalamus, decreased in the hyppocampus, and remained unchanged in medulla oblongata and cortex of cerebral hemispheres of hemiadrenalectomized rats after stress as compared to rats without stress. On the contrary, the intensity of specific GABA binding by synaptic membranes of medulla oblongata of hemiadrenalectomized rats was increased in response to stress effect it was decreased in the cortex of cerebral hemispheres, and remained unchanged in the hyppocampus.

[5'-Nucleotidase and adenosine deaminase activity in the rat brain upon prolonged effect of low radiation doses]. / Aktyvnist' 5'-nukleotydazy ta adenozyndezaminazy v mozku shchuriv za umov tryvaloho vplyvu iunizuiuchoho vyprominiuvannia nyz'koï intensyvnosti.

The effect of combined low radiation doses (0.2-50.8 cGy) on the 5'-nucleotidase and adenosine deaminase activities in the rat hypothalamus, hippocamp and cerebral cortex during 45, 120 and 365 days was examined. It has been shown that the changes in the 5'-nucleotidase activity of the hypothalamus and hippocamp have a phase character. The direction of the changes in enzyme activity of the hypothalamus and hippocamp adenosine forming was dependent on the zone stay period and had the exactly opposite character depending on the early and prolonged stay period in the zone. 5'-nucleotidase activity was changed under the influence of mean and lesser doses with an increase of the zone stay period. No changes in the 5'-nucleotidase activity of the cerebral cortex were noted. No changes in the hypothalamic adenosine deaminase activity of rats that stayed in a zone during 45 days were revealed; under the effect of mean dose during 120 days the activity decreased and also in case of a higher dosage during one year. The adenosine deaminase activity in animal hippocamp decreased in rats only under the influence of the lesser dose, for 45-day period. The decrease in adenosine deaminase activity of the cerebral cortex that was noted under the effect of all the three doses during 45 days, the higher and mean doses during 120 days disappeared in a year.

[Glutamate decarboxylase activity and GABA binding by synaptic membranes of brain structure under stress in intact rats and rats with hormonal blockade of the hypothalamo-hypophyseal-adrenal cortex system]. / Glutamatdekarboksilazna aktyvnist' ta zv'iazuvannia GAMK synaptichnymy membranamy struktur mozku za umov stresu v intaktnykh shchuriv ta shchuriv iz gormonal'noiu blokadoiu sistemy gipotalamus-gipofiz-kora nadnyrkovykh zaloz.

Under the inhibition of hypothalamo-pituitary-adrenal system function, as a result of prolonged hydrocortisone administration, the normal neurochemical reaction to stress, i.e. stimulating the formation of GABA (mediator that is basic among responsible ones for the realization of stress-limiting brain function) was absent. In the medulla under such conditions an increase in the degree of GABA reception processes activation of comparing with the intact stressed rats was revealed and in the hippocamp of their changes was directivity reverse.

[Changes in the level of gamma-aminobutyric acid in the blood of children with thyroid diseases]. / Zminy vmistu hama-aminomaslianoï kysloty v krovi ditei z zakhvoriuvanniamy shchytovydnoï zalozy.

Blood GABA level was studied in children with thyroid disorders. Increase of GABA level was revealed in thyroid hyperplasia (11 degrees) and euthyroid goiters; in blood of children with diffuse toxic goiter there changes are much more significant. In children with thyroid cancer dramatic increase of GABA content was observed; in the nearest time following thyroidectomy blood GABA level decreased to low values, several mouths later it became normal, in a year and more it became elevated again. In blood from three children with congenital hypothyrosis the level of the mediator was decreased; no changes in GABA level were observed in children with autoimmune thyroiditis. Two hours after falling asleep blood GABA content lowered both in normal children and those with euthyroid goiter and thyroid cancer. The mediator level elevated sharply after finishing physical exercises in normal children and those with euthyroid goiter, while in children with thyroid cancer response of GABAergic system to physical exercises was opposite and in operated children it was absent.

[The interaction of the renin-angiotensin and enkephalinergic systems of the brain and hypophysis in normal rats and in experimental pathology of the hypothalamo-hypophyseal-adrenal complex]. / Vzaimodeistvie renin-angiotenzinovoi i énkefalinergicheskoi sistem mozga i gipofiza krys v norme i pri éksperimental'noi patologii gipotalamo-gipofizarno-nadpochechnikovogo kompleksa.

Administration of angiotensin-converting enzyme inhibitor captopril inhibited the activity of renin-angiotensin system (RAS), increased leukin-enkephalin level in the hypothalamus and adenohypophysis. The data obtained suggest that the enzyme is an important link in the mechanism of interaction between the renin-angiotensin and enkephalinergic systems in rats.

[The activity of the enkephalinergic systems of the brain and hypophysis in experimental hypocorticism]. / Aktyvnist' enkefalinerhichnoï systemy mozku ta hipofiza za umov eksperymental'noho hipokortytsyzmu.

Changes in activity of basic components of enkephalinergic system, leu-enkephalin contents, activity of enkephalin-hydrolysing enzymes (enkephalinases A and B, enkephalin aminopeptidases) and 3H-leu-enkephalin specific binding to opioid receptor in rat anterior and mediobasal hypothalamus, striatum, medulla oblongata and adenohypophysis have been analysed on experimental models of hypocorticoidism. No changes in brain and pituitary body leu-enkephalin contents following unilateral hypocorticoidism. No changes in brain and pituitary body leu-enkephalin contents following unilateral adrenalectomy were shown. Bilateral adrenalectomy resulted in two-phase character of neuropeptide level: a decrease of leu-enkephalin contents in hypothalamus, striatum and adenohypophysis on the 7th day and its increase to the normal level on the 10th day after the operation were revealed. A decrease of leu-enkephalin contents in rat brain on the 7th day following adrenalectomy occurred simultaneously with a decrease in enkephalin aminopeptidase activity and specific binding of labeled leu-enkephalin testifying to strengthening of enkephalin release form neurosecretory granules of brain structures following adrenalectomy. Important changes in leu-enkephalin contents, reception and inactive processes on the level of adenohypophysis and on the level of hypothalamus, striatum and medulla oblongata were detected by cortisol and ACTH administration in adrenalectomised animals.

[The effect of adenosine on the hypothalamo-hypophyseal-adrenal system]. / Vplyv adenozynu na hipotalamo-hipofizarno-nadnyrkovu systemu.

The effect of various doses of intraperitoneally administered adenosine on the content of corticotropin and corticosteroids on the blood plasma was studied in Wistar rats. Dependence of the effect exerted by adenosine on the hypothalamo-pituitary-adrenal system on its dose was demonstrated: 1 hour after nucleoside administration in a dose of 50 mg/kg corticotropin concentration increased; 1 hour after adenosine administration in a dose of 25 mg/kg the level of corticosteroids in the blood plasma decreased.

[The GABA-ergic system parameters of the adrenal cortex in animals with normal and stimulated steroidogenesis]. / Deiaki parametry HAMK-erhichnoï systemy kory nadnyrkovykh zaloz tvaryn u normi ta za umov stymuliatsiï steroïdohenezu.

Activity of glutamate decarboxylase, a GABA synthesis enzyme, and intensity of its reception in the adrenal cortex and hypothalamus of guinea pigs and rats with normal and stimulated steroidogenesis was investigated. It has been shown that in the adrenal cortex there is a metabolic system which provides GABA synthesis from glutamate and mechanisms of GABA reception by plasmatic membranes. Mediator synthesis in the adrenal cortex is subjected to seasonal changes, GABA synthesis and reception selectively vary with administration of ACTH, prolactin and maintenance of animals on a diet with an excess of potassium ions.

[Kinetic parameters of GABA receptor binding by rat adenohypophyseal membranes under conditions of modelling various corticosteroid and ACTH levels in the body]. / Kineticheskie parametry retseptornogo sviazyvaniia GAMK membranami adenogipofiza krys v usloviiakh modelirovaniia razlichnykh urovnei kortikosteroidov i AKTG v organizme.

Kinetic parameters of 14C-GABA specific binding by rat adenohypophyseal plasma membranes were studied in experiments on modelling various corticosteroid and ACTH levels in animal body. A single hydrocortisone injection did not change K alpha for high- and low-affinity GABA receptors, the number of the former (Bmax) increasing in this case. Repeated hydrocortisone injections were associated with K alpha reduction for high-affinity GABA receptors and a noticeable increase of K alpha for low-affinity receptors, with their number reducing. ACTH injection did not change the kinetic parameters of GABA binding with receptors. The number of high-affinity GABA receptors and their affinity reduced after removal of adrenals whereas the number of low-affinity receptors in this case was increasing. A single hydrocortisone injection to adrenalectomized rats had a normalizing effect on adenohypophyseal GABA receptors. Analysis of the results and changes in blood hormonal levels indicated that affinity changes in high-affinity receptors and changed number of low-affinity adenohypophyseal GABA receptors correlated with changes in ACTH and hydrocortisone changes.

[Isolation of steroid-binding proteins on new affinity adsorbents]. / Vydelenie steroidsviazyvaiushchikh belkov na novykh affinnykh adsorbentakh.

Steroid-binding proteins of human blood are extracted and investigated on corticosteroid-hydrazide-oxypropyl-adsorbents by the affinity chromatography. The role of structural changes in the matrix-spacer-ligand system for different types of adsorbents is studied as well as a dependence of sorption on pH and salt environment. A dependence of the protein sorption on the isolated hydrazide groups is revealed. It is shown that hydrocortisone displays the highest binding activity to the protein pool in the affinity electroimmunoassay while the substance S-Reichstein and its 16-alpha-methyl analog--the least one.

[Changes in the activity of the brain renin-angiotensin system and in the functional state of the pituitary-adrenal system of rats under the influence of captopril]. / Zminy aktyvnosti renin-anhiotenzynovoï systemy mozku ta funktsional'noho stanu hipofizarno-nadnyrkovoï systemy shchuriv pid vplyvom kaptoprylu.

While studying the effect of peroral captopril injections on the activity of renin-angiotensin system (RAS), the activity of angiotensin-converting enzyme (ACE) and angiotensin II content from anterior and mediobasal hypothalamus, medulla and adenohypophysis of intact rats has been established to decrease. Captopril administration decreases ACE activity which increases after hydrocortisone injection in rat medulla and striatum. Captopril results in no potentiation of hormonal effect in hypothalamus and in adenohypophysis where ACE activity decreases following hydrocortisone injection. A decrease in the RAS activity of brain structures and adenohypophysis induced by captopril administration to rats is accompanied by the inhibition of the activity in the pituitary-adrenal system. A decrease in ACTH level and in 11-hydroxycorticosteroids of the rat blood plasma has been determined after single captopril injection in the dosage of 10 and 50 mg/kg of body weight. Duration of the effect depends on the captopril dosage.

[The effect of GABA-ergic preparations on the function of the hypothalamo-hypophyseal-adrenal system in patients with Itsenko-Cushing disease]. / Vliianie GAMK-ergicheskikh preparatov na funktsional'noe sostoianie gipotalamo-gipofizarno-nadpochechnikovoi sistemy u bol'nykh bolezn'iu Itsenko--Kushinga.

The effect of aminalon, baclofen and valproic acid on the levels of ACTH and cortisol was investigated in 58 patients with Itsenko-Cushing disease. The effect of GABAergic drugs showed correlation with the basal level of blood GABA: with aminalon and valproic acid the effect was observed only in patients with a low level of GABA, with baclofen--in patients with a high level of GABA there was found a decrease in the level of ACTH, associated with a high level of cortisol.

[Formation of gamma-aminobutyric acid from glutamate and putrescine in rat hypothalamic and hippocampal synaptosomes and regulation of these processes by glucocorticoids]. / Obrazovanie gamma-aminomaslianoi kisloty iz glutamata i putrestsina v sinaptosomakh gipotalamusa i gippokampa krys i reguliatsiia étikh protsessov gliukokortikoidami.

It has been shown that single or multiple hydrocortisone and ACTH administrations to intact rats increased GABA content and its synthesis from glutamate and putrescine in synaptosomes of hypothalamus. The letter content was increased by single hormonal administration while multiple hormonal administration and adrenalectomy decreased it. Ornithine decarboxylase activity was increased by single hydrocortisone administration to intact animals, following adrenalectomy, and it was decreased by single hormonal administration to adrenalectomized rats. GABA synthesis in synaptosomes of hippocampus from putrescine was increased by single hydrocortisone and multiple hormonal administrations. GABA content was increased by multiple administration of both hormones and was decreased by adrenalectomy. Putrescine level was decreased by multiple hydrocortisone administration to intact and single administration to adrenalectomized rats; ornithine decarboxylase activity was decreased by multiple administration of both hormones.

[Polyamines in the hypothalamus and hippocampus after the changes in corticosteroid levels in rats]. / Poliaminy gipotalamusa i gippokampa pri izmenenii urovnia kortikosteroidov v organizme krys.

Adrenalectomy as well as single or multiple hydrocortisone and ACTH administration have been studied for their effect on putrescine, spermidine and spermine contents, ornithine decarboxylase and S-adenosyl-+methionine decarboxylase activities in the rat hypothalamic and hippocampal tissues and fraction of nervous endings. The data obtained prove complicated character of changes in polyamine metabolism in the studied structures when glucocorticoid level is disturbed. Hormone action is characterized by regional and intracellular specificity and depends upon the ratio of administration and the initial hormonal background of the organism. The significance of these changes for feedback regulation of ACTH secretion and metabolism of GABA is discussed.

[The gamma-aminobutyric acid content of the blood plasma in patients with Itsenko-Cushing disease and its dependence on clinical and hormonal indices]. / Soderzhanie gamma-aminomaslianoi kisloty v plazme krovi bol'nykh bolezn'iu Itsenko--Kushinga i ego zavisimost' ot klinicheskikh i gormonal'nykh pokazatelei.

The content of GABA was measured in blood plasma of 111 patients suffering from Itsenko-Cushing disease. In untreated females, the blood GABA content was noticeably lowered; during treatment it increased, reaching normal, on the average, in patients with a history of total adrenalectomy. The changes in the blood GABA content in male patients were marked to a less degree. In the persons with a history of total adrenalectomy the GABA content turned out higher than normal. The blood GABA content in patients was dependent on the age and disease standing. In males experiencing disease exacerbation, it was appreciably reduced. As compared to females, the degree of a negative correlation between the blood content of GABA and ACTH (or cortisol) in males was more pronounced. The correlation between the excretion of 17-HCS with urine and GABA blood content in men and women was reverse. Women manifested a positive correlation between the excretion of 17-HCS with urine and blood GABA content, whereas men between arterial pressure and blood GABA. The problem of potential disorders of the GABAergic brain system in patients afflicted with Itsenko-Cushing disease is under discussion.

[Specific binding of H3-GABA by synaptic membranes of hypothalamus and hippocampus in rats after adrenalectomy and administration of hydrocortisone and corticosterone]. / Spetsificheskoe sviazyvanie H3-gamma-aminomaslianoi kisloty sinapticheskimi membranami gipotalamusa i gippokampa krys posle adrenaléktomii i vvedeniia gidrokortizona i kortikotropina.

It has been shown that single hydrocortisone administration increased 3H-GABA binding by hypothalamic synaptic membranes. ACTH administration enhanced binding in both studied brain structures. Multiple hydrocortisone administration did not effect 3H-GABA binding by hypothalamic and hippocampal membranes, while multiple ACTH administration caused the decrease in mediator binding by hypothalamic membranes and increased its level in hippocampal membranes. Adrenalectomy did not change 3H-gaba binding and single hydrocortisone administration to adrenalectomized rats increased 3H-GABA binding only by hypothalamic synaptic membranes.

[Hormonal control of metabolism of gamma-aminobutyric acid in the rat hypothalamus and hippocampus]. / Gormonal'nyi kontrol' obmena gamma-aminomaslianoi kisloty v gipotalamuse i gippokampe krys.

It has been established that hydrocortisone administration increased the amount of total, free, bound and synaptosomal GABA in the hypothalamus, glutamate decarboxylase activity in the homogenate and synaptosomes and time of the mediator turnover. ACTH administration increased the GABA content and glutamate decarboxylase activity in synaptosomes. The total amino acid content and time of its turnover got higher only with single hormone administration. In the hippocamp hydrocortisone administration increased the total and free GABA contents, its turnover time, glutamate decarboxylase activity in the homogenate and decreased GABA-aminotransferase activity in the homogenate and synaptosomes. The GABA level in synaptosomes grew only with multiple hormone administration. Single administration of ACTH decreased the total GABA content, glutamate decarboxylase activity in the homogenate, while its multiple administration increased the GABA level in synaptosomes followed by a decrease of GABA-aminotransferase activity in the homogenate and synaptosomes. The GABA turnover time fell with single hormone administration and grew with the multiple one. Adrenalectomy induced no changes in the GABA content and activity of its metabolism enzymes in the hypothalamus, however the bound GABA level decreased, while the turnover time increased. In the hippocamp adrenalectomy decreased total, free and synaptosomal GABA contents, glutamate decarboxylase activity in a homogenate and turnover time. Subsequent hydrocortisone administration only partly normalized the revealed changes of the GABA metabolism in the brain structures under adrenalectomy.

[Subcellular distribution of adenosine system enzymes in the hypothalamus and hippocampus of the rat brain]. / Subkletochnoe raspredelenie nekotornykh fermentov sistemy adenozina v gipotalamuse i gippokampe golovnogo mozga krys.

The subcellular distribution of 5'-nucleotidase and adenosine deaminase in rat brain hypothalamus and hippocampus was studied. In the hippocampus the 5'-nucleotidase activity was shown to be much higher than in the hypothalamus, while the adenosine deaminase activity, contrariwise, is nearly two times as high as that in the hypothalamus. During the analysis of subcellular distribution 5'-nucleotidase and adenosine deaminase were detected in all fractions under study, i. e., in nuclear, soluble, myelin fractions as well as in synaptic membranes, synaptosomes and "pure" mitochondria. The highest 5'-nucleotidase activity was found in the myelinic and synaptic fractions both in the hypothalamus and in the hippocampus. The highest adenosine deaminase activity was detected in the soluble fraction of the above structures. The enzyme activity in synaptic membranes and synaptosomes was nearly two times as low.

[Effects of desoxycorticosterone on 5-nucleotidase and adenosine deaminase activity in the hypothalamus and hippocampus of the rat brain]. / Vliianie dezoksikortikosterona na aktivnost' 5'-nukleotidazy i adenozindezaminazy v gipotalamuse i gippokampe golovnogo mozga krys.

Influence of single (enzyme activities was determined 5h after the preparation) and multiple (for 7 days) DOCA administration on 5'-nucleotidase (EC 3.1.3.5) and adenosine deaminase (ES 3.5.4.4) activities in homogenate and subcellular fractions of the hypothalamus and hippocampus of the rat brain has been studied. It has been shown that DOCA enhances adenosine metabolism in the hypothalamus activating both the enzymes while in the hippocampus 5'-nucleotidase activity increases whereas adenosine deaminase activity decreases. Possible ways of mineralocorticoid effects on adenosine system and the role of this nucleoside in these hormones mechanism of action on CNS functional activity are being discussed.

[The effect of hydrocortisone on the activity of 5'-nucleotidase and adenosine deaminase in the hypothalamus and hippocampus of the rat brain]. / Vliianie gidrokortizona na aktivnost' 5'-nukleotidazy i adenozindezaminazy v gipotalamuse i gippokampe golovnogo mozga krys.

The effect of single (1.4 and 24 h) and long-term (7 days) hydrocortisone intramuscular administration (5 mg/100 g of body mass) on 5'-nucleotidase and adenosine deaminase activities in homogenate and subcellular fractions of the rat brain hypothalamus and hippocampus has been studied. Enzymatic activity of adenosine metabolism in hypothalamus and hippocampus has been shown to undergo changes with the duration of hydrocortisone administration. A possible role of adenosine in the mechanism of glucocorticoid action in the CNS and the regulation of the hypothalamic-pituitary-adrenal axis is under discussion.