[Effects of the platelet activating factor on the proliferation and IgE secretion by U-266BL human myeloma cells].

Platelet activating factor (PAF) influences the proliferation and IgE secretion by U-266BL human myeloma (HM) cells. At a relatively high PAF concentration (up to 10(-8) M), the rate of proliferation is significantly decreased, while the IgE secretion rate is increased. At low PAF concentrations (10(-11) M), the HM cell proliferation rate increases, whereas their ability to IgE secretion decreases. The specific secretion activity (per cell) is a linear function in the range of PAF concentrations from 10(-11) to 10(-8) M. This behavior can be used for the quantitative determination of PAF in biological media.

[Effect of 1,2,3,4-tetrahydroimidazo[4,5-c]pyridine and 1,2,3,4-tetrahydroisoquinoline derivatives on the behavior and the brain receptor system in rats].

Adducts obtained via the interaction of formaldehyde with histidine (1,2,3,4-tetrahydroimidazo[4, 5-c]pyridine-3-carboxylic acid (I)), tyrosine (7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (II)), and dopamine (6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (III)) influence the behavior and the state of the brain receptor system of rats upon chronic administration (10-day treatment at a daily dose of 50 mg/kg, i.p.). All the compounds studied decrease the horizontal and (to a lower extent) vertical motor activity and increase the quiescence period duration. On the other hand, the effects of compounds tested on the vegetative reactions were different: compounds I and III increased, whereas compound II decreased these reactions. Using the radioligand binding method, it was established that the treatment with compound I led to a decrease in the density of benzodiazepine receptors (B max of [3H]-flunitrazepam was 78% of the control level) and to a significant (148%) increase in the density of specific binding sites for [3H]-spiperone (reflecting the total density of dopamine (D2) and serotonin (5-HT2) receptors. The chronic administration of compound III produced a reliable decrease (76% of the control level) only in the density of benzodiazepine receptors. None of the tested compounds influenced the affinity of receptors with respect to the radioactive ligands used.

[The action of korazol on the defensive behavior of rats]. / Vliianie korazola na oboronitel'noe povedenie krys.

The paper shows the dependence of behavioral changes provoked by corazol on individual characteristics of the animals. The rats with high activity in the ATS demonstrated the highest response to the drugs.

[Changes in the emotionally conditioned behavior of rats under the influence of the hexapeptide fragment GLLDLK of the protein inhibitor of diazepam binding]. / Izmenenie émotsional'no obuslovlennogo povedeniia krys pod deistviem geksapeptidnogo fragmenta GLLDLK belka--ingibitora sviazyvaniia diazepama.

It is shown that suboccipital injection of 100 micrograms of the gexapeptide GLLDLK (the fragment of endogenous peptide--the inhibitor of diazepam binding) modified (for 1-3 days) the emotionally conditioned behaviour of the rats (the test of "emotional resonance"). This modification was realized in some reinforcement of different behavioural patterns and had signs of anxiety and depression. In the test "social hierarchy" the injection of GLLDLK didn't change significantly the hierarchy in the whole rat society, but in the recipient behaviour the exploratory activity has been changed, the time of grooming increased and the quantity of social contacts decreased.

[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.

[Effect of amino acid derivatives of beta-carboline on the evoked activity of hippocampal neurons]. / Vliianie aminokislotnykh proizvodnykh beta-karbolina na vyzvannuiu aktivnost' neironov gippokampa.

The action of methylamide-beta-carboline-3-carboxylate (1), glycinamide-beta-carboline-3-carboxylate methyl ester (2), leucinamide-beta-carboline-3-carboxylate methyl ester (3) on evoked activity of hippocampal neurons was investigated using brain slice technique. Both 1 and 2 application (5 mkM, 15 min) reduced paired-pulse inhibition (PPI). Single-pulse and frequency stimulation revealed population spike (PS) increase or generation of additional PS after 1 or 2 application, the former drug being more active at all stimulation patterns. 3 had no definitive activity in the test-system used. The data obtained suggest similarity of pharmacological profiles of 1 and 2, and anxiogenic activity of 2 in vivo.

[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.

[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).