Effects of drotaverine hydrochloride on viability of rat cultured cerebellar granulocytes.

The neurocytotoxic effect of drotaverine hydrochloride was studied in culture of rat cerebellar granulocytes. Incubation of cells with 100 and 250 µM drotaverine reduced neuronal survival to 60 and 4%, respectively.

Cytostatic activity of peptide extracts of medicinal plants on transformed A549, H1299, and HeLa Cells.

Biological activity of peptide extracts of medicinal plants was studied on transformed non-small-cell lung carcinoma A549 cells, lung cancer H1299 cells, and cervical cancer HeLa cells at various cell densities. Cell survival and proliferation were evaluated 72 h after treatment with extracts in concentrations of 0.05, 0.25, and 0.5 microg/microl. The cytostatic effect was produced by peptide extracts of Camelia sinesis Kuntze, Inonotus obliquus, and a mixture Inula helenium L., Chelidonium majus L., Equisetum arvense L., and Inonotus obliquus. Peptide extracts of Hypericum perforatum L. and Laurus nobilis L. in the same concentrations had no effects on proliferative activity and growth of tumor cells.

[Antitumor activity of the plant remedy peptide extract PE-PM in a new mouse T-lymphoma/eukemia model].

A new mouse ASF-LL model of adult T-lymphoma/leukemia (ATLL) in humans was characterized by cytological, histopathological, and flow cytometry analyses. Encouraging similarities of morphological, pathological, and clinical signs were found. These included characteristic flower appearance of leukemic cells, lymphadenopathy and hepatosplenomegaly, multiple growths in the skin, urogenital tissues, lungs and pituitary gland, CD4+CD25+ phenotype of the majority of tumor cells that were selectin-L positive, a rapid clinical course, and poor response to standard chemotherapy. Plant peptides obtained from the traditional Russian herbal medicine have gradually gained considerable attention as a new source of anticancer drugs. We have tested antitumor activity of a peptide extract PE-PM obtained from a mixture of Chelidonium majus L., Inula helenium L., Equisetum arvense L. and Inonotus obliquus in new mouse T-lymphoma/leukemia model ASF-LL. Distinct antitumor activity of two local injections of the peptide extract PE-PM was detected by tumor growth inhibition and survival improvement of 33% of recipients bearing intraperitoneal form of ASF-LL.

Evaluation of antitumor activity of peptide extracts from medicinal plants on the model of transplanted breast cancer in CBRB-Rb(8.17)1Iem mice.

We studied antitumor effects of peptide extracts from plants on slowly growing mammary adenocarcinoma in CBRB-Rb(8.17)1Iem mice used as a model of breast cancer in humans. The antitumor effect of a single injection of the test peptides was evaluated by the delay of the appearance and growth of palpable breast cancer in mice over 4 weeks. Peptides from Hypericum perforatum and a mixture of Chelidonium majus L., Inula helenium L., Equisetum arvense L., and Inonotus obliquus exhibited maximum activity. Peptide extracts from Frangula alnuc Mill. and Laurus nobilis L. were less active. No antitumor effect of Camelia sinesis Kuntze was detected.

[Conformational analysis of cysteine-containing peptides and prospects of their application to 213Bi chelating in antitumor therapy].

The method of conformational analysis was applied to the spatial structures of peptide analogues of phytochelatins and some fragments of metallothioneins: (Cys-Gly)3, (Cys-Gly)3Asp, (Cys-Gly)3Glu, (Cys-betaAla)3, (Cys-gammaGlu)3, and (Cys-Gly-Gly)3. All the possible low-energy conformations of the molecules were revealed and the role of intra- and inter-residual interactions in the formation of their spatial structures was determined. A different tendency of the molecules under study for acceptance of conformations favorable for binding bismuth ions was shown. Low-energy structures providing an optimum binding of bismuth ion were shown to be most frequent for (Cys-betaAla)3 peptide. Among the analogues of peptide fragments of the metallothioneins, lacking in natural peptides, low-energy pentapeptide CCXXC fragments (where X = Gln, Asn, Phe, Tyr, and Gly) were revealed. In the alpha-helical conformations of these pentapeptides, the distance between the sulfur atoms corresponds to that in Bi2S3. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2006, vol. 32, no. 3; see also http://www.maik.ru.

[Analysis of peptides from animal and plant tissues]. / Analiz peptidov iz tkanei zhivotnykh i rastenii.

A new technique was developed for the analysis of peptide compositions of extracts from various animal and plant tissues. It involves the acidic extraction of a peptide fraction from the starting material and its precipitation with acetone, fractionation of peptides by ion-exchange chromatography by using a stepwise elution of fractions and detection by means of ninhydrin color reaction, and computer processing of the results. For the presentation of the results of analysis, chromatographic profiles and peptidograms were proposed. The results of analysis can be stored in a database and used for the creation of "generalized peptide portraits" and "differential peptide portraits" of the subjects investigated, which allow the identification of peptides characteristic of the subjects. The amount of peptide undergoing analysis ranged from 1 to 10 nmol.

Chemical heterogeneity of [3H]imipramine binding sites on human platelet membranes.

Functional groups essential for high- and low-affinity [3H]imipramine (IMI) binding were determined by the method of chemical modification. The high-affinity recognition sites contained cysteine and lysine amino acid residues, but not aspartic or glutamic acid residues. The low-affinity recognition sites contained only cysteine residues. Moreover, probably only part of these sites contained these residues. The arginine, tyrosine and histidine residues are not likely to be functionally important for the [3H]IMI binding process. Analysis of the structure-function interaction of drug molecules reveals that, for all substances with high displacement ability, there is a conformation in which they can react with high-affinity IMI recognition sites. Data obtained allowed us to construct a tentative structure model of the high-affinity recognition IMI binding site.

[Effect of nucleotides on N-methylcytisine and dimethyltubocurarine binding by the nicotinic acetylcholine receptors of the optic ganglia in the squid B. magister]. / Vliianie nukleotidov na sviazyvanie N-metiltsitizina i dimetiltubokurarina nikotinovymi atsetilkholinovymi retseptorami zritel'nykh gangliev kal'mara B. magister.

The effect of nucleosides mono-, di-, and triphosphates on binding of 3H-N-methylcytisine and 14C-tubocurarine to nAChR from squid optical ganglia were investigated. It was found, that ATP and GTP potentiate the specific binding of 3H-N-methylcytisine and inhibit the one of 14C-tubocurarine. While conducting the photoaffinity modification of nACHR by 3H-azidomethylcytisine in the presence of ATP the increase of specific incorporation of label was observed in comparison with control. Molecular weight of labeled receptor complex and subunit, carrying the binding site was the same as the original.

[Effect of amino acid derivatives of beta-carboline-3-carboxylate on rat behavior]. / Vliianie aminokislotnykh proizvodnykh beta-karbolin-3-karboksilata na povedenie krys.

It was shown, that administration of methyl ether N-(beta-carboline-3-carbonyl)-glycine (GA) at dose level of 1-10 mg/kg markedly reduced exploratory behavior and motor activity in the open field test and facilitated manifestation of different rats defend reaction types. Methyl ether N-(beta-carboline-3-carbonyl)-leucine (LA) at the same doses was less effective. Besides GA (10 mg/kg) like earlier described anxiogenic compound FG 7142 suppressed isolation induced muricide behavior of rats. The results obtained combined with literary data allow us to conclude, that GA possesses expressed anxiogenic activity.

[N-methylcytisine--a selective ligand of nicotinic receptors of acetylcholine in the CNS]. / N-metiltsitizin--selektivnyi ligand nikotinovykh retseptorov atsetilkholina v TsNS.

The ability of cytisine and its N-methyl derivatives to bind to nicotinic acetylcholine receptors (nAChR) from different tissues was studied. Cytisine and N-methylcytisine have high affinity (KD = 50 nM) to nAChR from squid optical ganglia. N,N-dimethylcytisine did not show high affinity to this receptor. In the case of nAChR from T. marmorata, cytisine was the only effective inhibitor of 14C-tubocurarine specific binding (Ki = 700 nM). N-methyl- and N,N-dimethylcytisine did not displace 14C-tubocurarine at a concentration of 0.1 mM. The results obtained indicate that there are some differences in the structure of nAChR binding sites from squid and T. marmorata optical ganglia.

[Comparative study of the effect of 3-carboxy-beta-carboline methylamide and diazepam on rat behavior]. / Sravnitel'noe izuchenie vliianiia metilamida 3-karboksi-beta-karbolina i diazepama na povedenie krys.

The effects of benzodiazepine receptor agonist, diazepam, and inverse agonist, FG 7142, were examined. Strong antagonism between FG 7142 (10 mg/kg) and diazepam (1 mg/kg) activity was revealed in the open field test. On the other hand, both FG 7142 and diazepam inhibited isolation-induced intraspecies aggressive behaviour of rats. FG 7142 also reduced interspecies aggression of mouse-killing rats. The findings suggest that both diazepam and FG 7142 have antiaggressive properties in the isolation-induced aggression model, which are mediated by benzodiazepine receptors of the central nervous system.

High- and low-affinity [3H]imipramine binding sites on human platelets: separate determination and involvement of sulphur-containing bonds.

We have confirmed the presence of two different classes of [3H]imipramine ([3H]IMI) binding sites on human platelets: high-affinity (Kd = 0.52 nM, Bmax = 1670 fmol/mg protein) and low-affinity (Kd = 101 nM, Bmax = 8,000 fmol/mg protein) binding sites. The high-affinity component of [3H]IMI binding can also be obtained separately as the difference between specific [3H]IMI binding in Na-containing and Li-containing incubation buffer. The low-affinity component can be obtained as the difference between [3H]IMI binding in 50 mM Tris-HCl, 5 mM KCl, 120 mM LiCl, (pH 7.5) in the absence and presence of 0.1 mM IMI. The chemical modification of SH groups was performed with Ellman's reagent (10 mM, 40 min at 23 degrees C). The high-affinity component of the binding was totally inhibited while the low-affinity component only decreased by 39%. No decrease in [3H]IMI specific binding was observed when the modification of SH groups was carried out in the presence of 1 microM IMI. The inhibition of high- and low-affinity [3H]IMI binding was reversible since it was completely restored by incubation of modified membranes with 1,4-dithioerythritol (DTE). The reduction of SS groups by DTE (10 mM, 1 h at 23 degrees C) in the intact membrane preparation produced an increase in total number of binding sites of the high-affinity component of [3H]IMI binding by 50%.

[Gliotrophic effect of the total peptide fraction isolated from the urine of healthy subjects and patients with manic-depressive psychosis]. / Gliotroficheskoe vliianie summarnoi peptidnoi fraktsii, vydelennoi iz mochi zdorovykh liudei i bol'nykh maniakal'no-depressivnym psikhozom.

The authors studied the effect of the total peptide fraction of the urine of healthy donors and patients with manic-depressive psychosis on the development of glioneuronal aggregates of the cerebral cortex cultivated in collagen gel. Urine peptides from the patients dramatically increased the migration and differentiation of glioblasts while the action of healthy donors' peptides was less marked. The growth of neurites under the effect of peptides significantly differed from the control values.

[Structural characteristics of the recognition site of cholinergic ligands of the nicotinic acetylcholine receptor from squid optic ganglia]. / Strukturnye osobennosti uchastka uznavaniia kholinergicheskikh ligandov nikotinovogo retseptora atsetilkholina zritel'nykh gangliev kal'mara.

The effect of chemical modification on the binding of cholinergic ligands to nicotinic acetylcholine receptor from squid optical ganglion was studied. The existence of two chemically distinct subpopulations of binding sites was postulated. Subpopulation I contains, in all probability, Arg, Tyr and carboxyl groups critical for the binding of both ligands. Subpopulation II differs from the first one in the amino group present instead of Arg. The amino group important for the binding of d-tubocurarine alone was found in both subpopulations. The data obtained allow one to construct a model of nicotinic acetylcholine receptor cholinergic ligand recognition sites.

[Comparative study of the muscarinic cholinoreceptors of the glial cells in the human and rat cerebral cortex]. / Sravnitel'noe izuchenie muskarinovykh kholinoretseptorov kletok glii kory mozga cheloveka i krysy.

Radioligand analysis was used to study and compare muscarinic cholino receptors from human and rat brain glial cells containing no neurospecific proteins. It was demonstrated that 3H-quinuclidinyl benzylate has a higher affinity for muscarinic cholino receptors of human glia (Kd 2.0 nM) than receptors of rat glial cells (Kd 9.1 nM). By pharmacological properties muscarinic cholinoreceptors of the glia differ from receptors of insect brain and are similar to cholinoreceptors from animal brain synaptosomes.

[Pharmacological characteristics of the acetylcholine and L-glutamate receptors of the subpharyngeal ganglion neuron in the mollusk Zachrysia guanensis]. / Framakologicheskaia kharakteristika retseptorov atsetilkholina i L-glutamata neirona podglotochnogo gangliia moliuska Zachrysia guanensis.

The presence of acetylcholine and L-glutamate receptors sensitive to the cholinoreceptor-specific ligands cytizine and tubocurarine has been demonstrated by means of microapplication of acetylcholine and L-glutamate to the central parietal zone of the subpharyngeal ganglion of the mollusc Zachrysia guanensis. Azidocytizine inhibited the function of acetylcholine receptor but did not affect glutamate receptor. Based on the electrophysiological data and analysis of ligand conformations a model has been designed for a site where L-glutamine is recognized by glutamine receptor.

[Action of beta-carboline derivatives on the evoked activity of hippocampal neurons]. / Deistvie proizvodnykh beta-karbolina na vyzvannuiu aktivnost' neironov gippokampa.

The effects of tetrahydro-beta-carboline-3-carbonic acid methyl ester (I), 1-phenyl-tetrahydro-beta-carboline-3-carbonic acid methyl ester (II), tetrahydro-beta-carboline-3-carbonic acid methylamide, and beta-carboline-3-carbonic acid methylamide on evoked potentials (EP) of neurons were investigated in experiments with hippocampal slices. Each compound was tested in 5 experiments. These derivatives applied in a concentration 4 M had the following features in common: 1) a 10-20% augmentation of the amplitude of the population spike (PS) evoked in the CAI area by Schaffer collaterals stimulation; 2) appearance of additional PSs; 3) potentiation of the substance effect after beginning of washing; 4) poor washing (incomplete recovery of EP after 40-60 min of washing). In one of five experiments, I administration led to a decrease in the PS amplitude (by 15%). A similar effect was observed in one of five experiments during perfusion of II. The authors assume that there are hippocampal mechanisms responsible for realization of opposite effects associated with occupation of benzodiazepine receptors by ligands.

[Probable mechanism of recognition of cholinergic ligands by acetylcholine receptors]. / Vozmozhnyi mekhanizm uznavaniia kholinergicheskikh ligandov atsetilkholinovymi retseptorami.

Dryding's models were used for the conformational analysis of compounds affecting muscarin-specific acetylcholine receptor and nicotin-specific acetylcholine receptor. Ammonium group and ether oxygen (3.6 A apart from the ammonium group) specifically oriented to each other were shown to be necessary structural elements to reveal muscarin-type cholinergic activity. Ammonium group along with carbonyl oxygen or its substituent (5 A distance) are the necessary structural units providing nicotin-type cholinergic activity. The presence of two hydrophobic substituents (one in the ammonium area and the other neighbouring the second active grouping) is the additional factor. The developed principles were justified by the use of a series of synthetic samples. The compounds were obtained likely favouring affinitive modification of acetylcholine receptor (dissociation constants of acetylcholine receptor complexes equalling to 10(-4)--10(-7) M-1).