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Biomedical subjects

A V Kamernitskiĭ

Publications and source records attributed to A V Kamernitskiĭ.

At least 19 recordsLinked to original sources
PubMed1999

[Pentacyclic steroid analogs: interaction of 16 alpha,17 alpha-cyclopentanoprogesterone with rat uterus proteins].

Using 3H-labeled derivatives, kinetic parameters of specific binding of progesterone (I) and 16 alpha, 17 alpha-cyclopentanoprogesterone (II) to proteins of the uterus soluble fraction in rats were measured. It was shown that their affinities to proteins are comparable (K 10.5 +/- 2.4 and 6.7 +/- 3.4 nM for (I) and (II), respectively, upon 22 h incubation). The unlabeled compound (II) can displace [3H]progesterone from complexes with the protein with a concentration-independent efficiency corresponding to the ratio of K values for compounds (I) and (II). At the same time, the efficiency of the unlabeled progesterone in the displacement of [3H]compound (II) from protein complexes fell with an increase in the progesterone concentration. The concentration of high-affinity sites of [3H]compound (II) exceeded by 1.5 to 2 times the concentration of sites for [3H]progesterone. Dynamics of dissociation of proteins complexes of [3H]progesterone and 3H]compound (II) had a two-phase character with a decrease in the dissociation rate constants for both phases as the times of exposition of [3H]ligands to proteins grew. The ratio of slow- and fast-dissociating ligand-receptor complexes was thereby unchanged. These data suggest the presence in the rat uterus soluble fraction of two types of proteins differing in the capacity to recognize the additional five-membered ring D' in the steroid molecule.

Animals↗
PubMed1996

[Kinetics of interaction of [3H]16alpha,17alpha-cyclohexanoprogesterone with progesterone receptor in the rabbit uterus].

A discrepancy between high biological activity of 16 alpha,17 alpha-cyclohexanoprogesterone (pentarane) and its relatively low affinity for progesterone receptor was demonstrated previously; the present study revealed that this is not true and that the discrepancy was due to the overestimation of the effective ligand concentration during calculations of the Kd or relative binding affinity (RBA) because of high absorption of pentarane on the surface of test tubes; up to 70% of added ligand can thus be absorbed. Corrected RBAs of pentarane versus progesterone in progesterone receptor-binding assay are from 7 to 10 and do not depend on [3H]-labeled ligand used. Unlabeled steroids competitively inhibit binding of [3H]progesterone and [3H]pentarane with progesterone receptor. The Kd values are 27 and 2.5 nM at 0-4 degrees, respectively. Pentarane affinity to serum proteins is lower and its metabolism in the liver homogenate is more slow versus progesterone characteristics. D'-ring unsaturated pentarane analog 16 alpha,17 alpha-cyclohex-23-enoprogesterone completely inhibited specific binding of [3H]progesterone and [3H]pentarane to a cytosolic protein with similar efficiencies which were about 0.1 of pentarane efficiency. Thus, progesterone receptor is the only protein in the soluble fraction of rabbit uterus homogenate that specifically binds pentarane.

Animals↗
PubMed1991

[A new class of cardiotonic steroids].

A series of 23-oxosteroid derivatives have been synthesized and tested for their inhibiting Na+, K(+)-dependent ATPase from rat brain in the 1 x 10(-6)-1 x 10(-4) M concentrations. Natural 23-oxogenins from sea star Asterias amurensis and synthetic monoesters showed the inhibiting activity upto 50-55%. These compounds caused heart contraction in frogs at the level of the known cardiotonic strophanthin G, and inotropic activity on isolated heart of mollusk Spisula sachalinensis.

Animals↗
PubMed1990

[The in vivo production of corticosteroids by the adrenals in rats of the SSHR hypertensive strain].

The review contains the hormonal characteristic of the line of stress sensitive hypertensive rats (SSHR) developed from normotensive Wistar rats (WR) during genetic selection. The in vivo production mineralo- and glucocorticoids by rat adrenal glands is estimated. It is shown that SSHR have an increased level of glucocorticoids. The biochemical features of pathogenesis of essential hypertension are discussed.

Adrenal Cortex Hormones↗
PubMed1988

[Relation of the progestagenic activity and conformation of the 17beta-acetyl side chain in the D'6-pentarane series].

The synthesis of 2' beta-methyl-16 alpha,17 alpha-cyclohexanoprogesterone and its MM2 conformational analysis have been performed. The acetyl side chain was shown to have an unusual conformation with the torsion angle C13-C17-C20-O20 being -32.1 degrees. This conformation is by 5.4 kJ.mol-1 more stable than the usual one with the torsion angle 130.3 degrees. 2' beta-Methyl-16 alpha,17 alpha-cyclohexanoprogesterone proved to be inactive as a progestogen (pregnancy maintenance and McPhail tests). The lack of the activity may be due to the additional methyl group in D'-ring causing a change of the conformation of the 17 beta-acetyl side chain, thus hindering the formation of the conformation necessary for binding to the progesterone receptor.

Animals↗
PubMed1988

[Interaction of pregna-D'-pentaranes--pentacyclic derivatives of progesterone--with gestagen-binding sites of uterine cytosol].

The interaction of promegestone (R-5020), progesterone (P) and its derivatives having and additional carbocyclic D' (pregna-D'-pentrans) with progestin-binding cytosol system of the uterus was studied in different species (rabbits, rats, guinea-pigs and men). A comparative analysis of the competitive binding data for the mentioned compounds has shown interspecies differences in ligand specificity. Two types of binding sites for 3H-D'-pentran (in contrast to R-5020 and P) have been detected in rabbit uterus cytosol, both in intact and estrogenized animals. However, in rabbits, estrogenization altered the values of the apparent equilibrium constants and binding capacities. At the same time, the interaction of pentran with progestin-binding sites in guinea-pig and human uterus cytosol is nonspecific. It is suggested that the features of the interaction of 3H-D'-pentran with its binding sites in rabbit uterus cytosol may be determined by an increase in hydrophobic bond.

Animals↗
PubMed1986

[Progestagenic activity and the mechanism of the contraceptive action of mecygeprone].

Progestagenic activity of a modified analog of progesteron-6 alpha-methyl-cyclogexan-[1', 2', 16 alpha, 17 alpha]-pregn-4-en-3,20-dion including into mecygepron composition has been studied; its activity is proved to be 5 times as great as that of progesteron at any way of administration. Mecygepron affects processes of ovogenesis and early embryogenetic development in rats. A decreased number of washed out embryos is observed, while the number of lutein bodies specific for intact rats remains the same, decelerated rate of cleavage and increased number of unfertilized ova. In the mechanism of the changes observed an essential role plays a decreased secretion of lutropin resulting in a prolonged estrol cycle and, evidently, in intrafollicular overmaturation of the ova, which loose their ability to be fertilized. Besides, the disturbed hormonal balance under mecygepron influence can affect the character of the oviduct and uterine contents and, thus, prevent the normal development of the fertilized gametes.

Administration, Oral↗
PubMed1984

[The effect of the distribution of polar groups in a steroid molecule on its inhibition of Na+,K+-ATPase].

Transformed steroids having oxidized side chains in the D ring site and varying by polarity of the substituent at the ring A C(3)-position--acetates, glucosides or with free hydroxyls--in the concentration range 1 X 10(-4) - 1 X 10(-7) M were found to inhibit Na+, K+-ATPase. The extent of inhibition decreases with the rise in the polarity of the A region of the steroid molecule. With the compound devoid of polar groups in the D region an increase in the inhibitory activity is observed on passing from 3-acetate to 3-glucoside. The data obtained confirm the relationship between the extent of Na+, K+-ATPase inhibition and biphilicity of the molecule.

Cardiac Glycosides↗
PubMed1984

[Molecular polarity dependence of the transformed steroid effect on Na,K-ATPase].

The transformed steroids containing an additional cycle E (delta-lactone or 16.23-pyranone) or 23-carbethoxy side chain (1.10(-5) M) inhibit Na,K-ATPase from pig kidney medulla. The steroid structure has a noticeable effect on ATPase inhibiton varying from 9 to 35%. The data obtained suggest that the position, stereochemistry and the uneven distribution of polar substituents in the steroid molecule are essential for ATPase inhibition by steroid aglycons.

Animals↗
PubMedDate not supplied

[Species and tissue distribution specificity of proteins binding 16alpha,17alpha-cycloalkane derivatives of progesterone].

The binding of [3H]progesterone and [3H] 16 alpha,17 alpha-cycloalkanoprogesterones to proteins from rat, rabbit, and human uteri and other organs was studied. We found that 16 alpha,17 alpha-cycloalkanoprogesterone derivatives display affinities for the uterine progesterone receptors comparable with that of the natural hormone and no substantial species differences in the affinity. Rabbit uterus was found to have no proteins distinct from the progesterone receptor that specifically bind [3H] 16 alpha,17 alpha-cycloalkanoprogesterones. At the same time, in the human uterus, we found another protein that binds some of these progesterone derivatives; it turned out to be similar to the protein from rat uterus. A similar protein with the same selectivity and affinity for steroids was also found in rat and human kidneys. Blood serum, liver, lung, and a number of other tissues were found to contain a protein of the third type that binds the same 16 alpha,17 alpha-cycloalkanoprogesterones and exhibits submicromolar Kd values for these steroids and a very low affinity for progesterone. We speculated that the introduction of a bulky substituent adjacently to the 17 beta-side chain of progesterone could result in a change in the general biodynamics of the derivative including its transport, uptake, and accumulation in tissues, which may determine the selectivity of its effect.

Animals↗
PubMedDate not supplied

[The effect of pregna-D'-pentarans on myometrial contractile activity in pregnant rats].

The authors studied the effect of synthetic gestagens on spontaneous contractility of the myometrium in pregnant rats. The direction of the effect of progesterone and its analogs on the contractility is determined by stereochemistry of the linkage of rings A and B of the steroid molecule. Compounds possessing translinkage (5 beta-steroids) increase the amplitude of myometrium contraction, whereas their analogs with cms-coupling of rings A and B (5 alpha-steroids), and 4,5-unsaturated steroids reduce it.

Animals↗
PubMedDate not supplied

[Morphological changes in the rat uterine tissues exposed to pregna-D'-pentaran derivatives of progestins and anti-progestins].

Changes in the uterus morphology of mature female rats were studied on the model of pseudopregnancy after treatment with the progestin 16 alpha,17 alpha-cyclohexanoprogesterone (PR) and the antirpogestins 5 alpha(H)-16 alpha,17 alpha-cyclohexano-4,5-dihydroprogesterone (APR1) and 5 beta(H)-16 alpha,17 alpha-cyclohexano-4,5-dihydroprogesterone (APR2). The rats were preliminarily estrogenized with 17 beta-estradiol at a dose of 1 microgram/(animal day) for 4 days and then treated with PR at a dose of 0.2 mg/(animal day) for 14 days. The first group was then left without any treatment, whereas APR1 and APR2 were injected at the dose of 0.2 mg/(animal day) for 4 days to the animals of the second and the third groups, respectively. Light and electron microscopy of the uterus preparations demonstrated that the PR action provoked a complete pseudopregnancy picture characterized by the endometrium functionalization and the myometrium hypertrophy. Subsequent treatment with APR1 and APR2 caused the hypertrophy to cease, which had a more pronounced effect in the case of APR1. At the same time, some indications of the endometrium functionalization remained observable after treatment with APR1 and APR2. The specific binding sites for 3H-labeled APR1 and APR2 were absent from the uterus cytosol for the rats gestagenized with PR.

Animals↗
PubMedDate not supplied

[Effect of mineralocorticoid analogs on Na(+),K(+)-dependent ATPase].

The effect of 42 steroids of the 20-ketopregnane series with heterocycles fused in positions 16 alpha and 17 alpha on the activity of Na+,K(+)-activated ATPase from pig kidney was studied. It was shown that the studied compounds could be divided into two groups. The compounds from the first group stimulate the ATPase at low concentrations (1 x 10(-8)-1 x 10(-7) M) and inhibit it at high concentrations (1 x 10(-4) M). The second group of compounds stimulated the sodium pump at either concentration. This is explained by the cooperative action of the ATPase tetramer: after the reaction of its first binding site with the ligand, the tetramer changes the conformation and specificity of its other binding sites. Computer analysis of this series of compounds was carried out and a mathematical model of the dependence of their activities on the structure of their substituents was obtained with a high correlation coefficient and a satisfactory predictive power. This confirmed the structural similarity of the studied compounds with respect to their interaction with the ATPase binding sites. The method of descriptor analysis that was applied in this study is a new variant of approximation; it is based on the use of symbol variables as descriptors.

Algorithms↗