[Changes in the characteristics of glucocorticoid hormone binding in human peripheral blood lymphocytes during myocardial infarct]. / Izmeneniia kharakteristik sviazyvaniia gliukokortikoidnykh gormonov v limfotsitakh perifericheskoi krovi cheloveka pri infarkte miokarda.

Competitive binding was used to determine the number of binding sites to glucocorticoid hormones in peripheral blood leukocytes of normal subjects, patients with unstable angina pectoris and patients with myocardial infarction. A sharp (2-3-fold) increase in the number of binding sites was observed in patients with myocardial infarction during the first 24 hours after the onset of the disease.

[A factor which modifies the interaction of steroids with glucocorticoid receptors]. / Faktor, modifitsiruiushchii vzaimodeistvie steroidov s gliukokortikoidnymi retseptorami.

A mechanism which determines the difference in the ability of deoxycorticosterone (DOC) to inhibit the binding of 3H-triamcinolone acetonide (3H-TA) to glucocorticoid receptors of rat heart and liver cytosols was investigated. DOC was found to strongly inhibit the binding of 3H-TA by heart cytosol, but to exert only a slight inhibitory effect towards the live cytosol binding. This difference was not due to the influence of the enzymes sensitive to molybdate ions, the presence of DOC-degrading enzymes or contamination of liver cytosol by blood serum. The liver cytosol devoid of the glucocorticoid receptor activity by heating was found to contain a factor modifying the "in vitro" interaction of DOC with the heart cytosol glucocorticoid receptors (receptor modifying factor, RMF). This factor is coeluted with the high molecular weight fraction during gel filtration, is precipitated at 50-70% ammonium sulphate saturation, can be absorbed by DEAE-Sephacel from cytosol at pH 7.4 under hypotonic conditions and extracted at about 0.06 M KC1. The sensitivity to proteases and the lack of sensitivity to nucleases point to the proteinic nature of the factor. It was assumed that in terms of the interaction of some steroids with glucocorticoid receptors, the tissue specificity can, at least partly, be explained by the differences in RMF concentration.

[Accumulation by preparations of rat heart sarcolemma of protein-bound forms of glucocorticoids]. / Akkumuliatsiia preparatami sarkolemmy serdtsa krysy belkovosviazannykh form gliukokortikoidov.

The accumulation of free and protein-bound forms of [3H]corticosterone and [3H]dexamethasone by preparations of heart sarcolemma from adult male Wistar rats was studied. At physiological concentrations of glucocorticoids the sarcolemma preparations showed a considerably greater accumulation of the cytosol-bound form of glucocorticoids as compared to the free form. On the contrary, the formation of [3H]corticosterone-transcortine complex decreased the steroid uptake by the membranes under these conditions. The [3H]steroid-albumin complexes obtained by incubation of very high concentrations of [3H]glucocorticoids with pure albumin were retained by the membranes better than the free form of the hormones. The differences in the accumulation by membranes of steroid--cytosol and steroid--albumin complexes during temperature rise from 0 degrees to 20 degrees C were found. The increase in the uptake of steroid--cytosol complexes was evidently caused by thermal "activation" of the complexes, while the temperature influence on the steroid--albumin complexes accumulation by sarcolemma preparations was directly due to the uptake process. An addition of molybdate (blocker of steroid--receptor complexes activation) at a concentration of 100 mM completely eliminated the thermal effect on the steroid--cytosol complexes accumulation.

[Propranolol beta-blocker decrease in the concentration of high-affinity binding sites for calcium ions by sarcolemma membranes of the rat heart]. / Snizhenie beta-blokatorom propranololom kontsentratsii vysokoaffinnykh uchastkov sviazyvaniia ionov kel'tsiia sarkolemmal'nymi membrananmi serdtsa krysy.

In vivo administration of propranolol considerably inhibits the isoproterenol-stimulated increase in 45Ca accumulation by the myocardium and completely eliminates the potentiation of isoproterenol effect by hydrocortisone. A significant lowering of the concentration of high affinity binding sites for calcium in the sarcolemmal membranes can be produced by propranolol in vitro. Under these conditions, the glucocorticoids do not change the sarcolemmal Ca2+-binding parameters or modulate the propranolol effect. Therefore, for the manifestation of glucocorticoid action to be brought about, the integrity of the cells is apparently required, while propranolol seems to change calcium binding by direct interaction with the sarcolemmal membranes. It is suggested that in vivo propranolol inhibition of catecholamine effect on calcium ion accumulation by the myocardium depends on the interaction with the beta-receptors and direct modulation of the concentration of high affinity binding sites for calcium ions on the surface of the sarcolemma.

[Evidence for the presence of glucocorticoid receptors in heart contractile cells]. / Dokazatel'stvo nalichiia retseptorov gliukokortikoidov v sokratitel'nykh kletkakh serdtsa.

Using 3H-labelled glucocorticoids, the receptor activity of heart and liver cytosol preparations from various animal classes and species, the distribution of receptors in the myocardium from different divisions of rat heart and the number of glucocorticoid receptors in the myocyte preparations isolated from adult rat hearts after treatment of cardiac tissue with hyaluronidase and collagenase have been studied. The specific binding of 3H-dexametasone to bovine fetal heart endothelial cells as well as to some other cell cultures was investigated. The data obtained suggest that the bulk of the total receptor activity of the heart is accounted for contractile cells of the myocardium. The number of specific sites of glucocorticoid binding by whole myocyte cells (per 1 mg of protein) or by "crude nuclear fraction" (per 1 mg of DNA) is comparable to that for some other cell types, which are believed to be hormone-sensitive. However, by the number of receptors per single cell myocytes surpass all the other cell types under study.

[Heterogeneity of cardiac glucocorticoid receptors]. / Geterogennost' gliukokortikoidnykh retseptorov serdtsa.

The work presents the main results obtained in the investigation of properties and distribution of the glucocorticoid cardiac receptors as well as mutual conversions of different forms of the glucocorticoid-receptor complexes. The receptors have been found in hearts of various kinds of animals. The glucocorticoid receptor activity is distributed approximately evenly in the myocardium of the left and right ventricles and auricles. The receptors have been found both in isolated myocytes and in endothelium cells. Methods of chromatography can successfully be used in decomposition of the glucocorticoid-receptor complex to heterogenic components. The role of some factors in the mechanism of the functioning of the receptor system is discussed.

[Corticosteroids and the adrenaline activation of glycogen phosphorylase in heart tissue]. / Kortikosteroidy i aktivatsiia adrenalinom glikogenfosforilazy v serdechnoi tkani.

Study of changes in the glycogen phosphorylase activity under the effect of adrenaline in the hearts of intact, adrenalectomized and sham-adrenalectomized rats demonstrated that stress increased the phosphorylase A level considerably. Against the background of these changes perfusion of the heart with 0.5.10(-7)M adrenaline produced no further elevation of the enzyme activity. Following restoration of the basal phosphorylase A to the normal level adrenaline again acquired the capacity to Phosphorylase activation. Stable absence of response of the heart tissue to adrenaline by increase of phosphorylase A activity was noted on the 5th postadrenalectomy day; this apparently followed disturbances in the potassium ions accumulation in the cells.

[Calcium and the permissive effect of glucocorticoids: the role of glucocorticoids in an adrenaline-induced increase in the rate of calcium absorption by the ventricular tissue of the rat heart]. / Kal'tsii i permissivnyi éffekt gliukokortikoidov: o roli gliukokortikoidov v indutsiruemom adrenalinom uvelichenii skorosti pogloshcheniia kal'tsiia tkan'iu zheludochkov serdtsa krys.

It was demonstrated in rat experiments that the ability of the myocardial ventricles to increase 45Ca absorption after the injection of adrenaline was disturbed on the 3rd--5th day following adrenalectomy. The decrease in sensitivity to adrenaline occurred in two phases and was delayed essentially after a fall in the concentration of glucocorticoids in circulation. Chronic in vivo injection of hydrocortisone (2.5 mg per rat) into these animals for 3--5 days restored the effect of catecholamine to a great extent. The restorative effect was weaker when the rats were given a single intravenous hydrocortisone infusion 6 hours before being killed. Increase of the single intravenous dose of the hormone to 5 and 7.5 mg per rat reduced its effect. The authors assume that the described permissive effect of glucocorticoids is determined not by their direct interaction with the cytoplasmic membrane but by hormone induced intracellular synthesis of proteins capable of participating in the regulation of permeability to ions.

[Activation of glucocorticoid cytoreceptors in rat heart]. / Aktivatsiia gliukokortikoidnogo tsitoretseptora serdtsa krysy.

Accumulation of 3H-dexamethasone by the nuclei in a cell-free system was studied. The increase in temperature from 0 degrees to 20 degrees C and treatment of cytosol by KCl (0.4 M) or theophylline (10mM) significantly increased the absorption the bound hormone by the nuclear fraction. Activation of the steroid-protein complex induced by temperature and addition of theophylline did not change its size. The increase in the ionic strength decreased the Stokes radius from 53 A down to 39.5 A and the sedimentation coefficient value from 7S down to 4S. It is concluded that the heart tissue cytoplasm contains a glucocorticoid receptor.

[Binding of glucocorticoids by a transcortin-like protein in the cytoplasmic fraction of rat myocardium]. / Sviazyvanie gliukokortikoidov transkortinopodobnym belkom tsitoplazmaticheskoi fraktsii miokarda krys.

Myocardial cytosol of adult adrenalectomized rats bound specifically 3H-corticosterone and 3H-hydrocortisone and did not bind the synthetic 9alpha-fluoroglucocorticoid (dexamethasone) in vitro at 0-4 degrees. The specific binding of dexamethasone was not also found in the cytosol of neonatal rats. Heating of myocardial cytosol of adrenalectomized rats within 10 min at 60 degrees led to the complete loss of the glucocorticoid-binding activity. Treatment of the cytosol within the same period but at the temperature lower than 55 degrees did not affect its binding capacity. 3H-corticosterone-cytoreceptor complex was precipitated by ammonium sulphate at 40-60% of saturation. The complex was eluted from a column of Sephadex G-150 by solutions with both low (0.015 M KCl) and high (0.4 M KCl) ionic strength as the alone peak. This fraction corresponded by molecular weight to the transcortin complex. The data obtained and the results of our previous investigations suggest that myocardial glucocorticoid-binding cytoplasmic protein is related to transcortin-like cytoreceptors.