Peptide regulation of specific ligand-receptor interactions of GABA with the plasma membranes of nerve cells

V’yunova, T. V.; Андреева, Л. А.; Шевченко, К. В.; Шевченко, В. П.; Myasoedov, N. F.

doi:10.1134/s1819712414040114

Cited by 9 publications

(9 citation statements)

References 32 publications

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“…The radioligands were checked for stability of their chemical structure within the incubation period (up to 120 min), using HPLС method of analysis. The characteristic of [ 3 H]GABA specific binding to rat brain cells' plasmatic membranes was obtained in our previous study; within the present experimental conditions, we got the same results (Table ). Two sites of [ 3 H]GABA specific binding were found in all the tested brain structures (hippocampus, cerebellum, cortex, and basal nuclei) and characterized by the same affinity.…”

Section: Resultsmentioning

confidence: 99%

“…Each biologically active neuropeptide is characterized by a unique spectrum of molecular receptor and physiological activity. For example, in contrast to Semax (nootropic and neuroprotector), peptide anxiolytic Selank potentiates the binding of [ 3 H]GABA in the presence of peptide molecules (“in vitro”) and increases the number of [ 3 H]GABA binding sites after pre‐introduction . Somatostatin, depending on its concentration, is able to modulate (potentiate or inhibit) ion currents of rat hippocampal neurons glutamate and GABA receptors …”

Section: Discussionmentioning

confidence: 99%

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An integrated approach to study the molecular aspects of regulatory peptides biological mechanism

V’yunova

Andreeva

Шевченко

et al. 2019

Labelled Comp Radiopharmac

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An integrated methodological approach to study the molecular aspects of short regulatory neuropeptides biological mechanism is proposed. The complex research is based on radioligand-receptor method of analysis and covers such points of peptides molecular activity as: specific binding of peptides to brain cells plasmatic membranes, formation of tissue specific synacton, influence of peptides (as allosteric modulators) on functionality of different neuroreceptors as well as delayed in time effects of peptides on receptor-binding activity of well-known neuroreceptor systems. Radiolabeled ligands in such complex study are the one of the best and precision instruments to uncover the molecular mechanism of multiple and multitarget biological effects of regulatory peptides. In this issue we used heptapeptide Semax as a model regulatory peptide, [ 3 H]Ach and [ 3 H]GABA as an effector molecules, and the rat model of stress-induced memory and behavior impairment as a morbid state. We showed the ability of Semax to modulate in a dose-dependent manner [ 3 H] Ach and [ 3 H]GABA specific binding to some of its corresponding receptors as well as to affect the number of [ 3 H]GABA specific binding places on rat neurons plasmatic membranes after complex stress exposure.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An integrated approach to study the molecular aspects of regulatory peptides biological mechanism

V’yunova

Andreeva

Шевченко

et al. 2019

Labelled Comp Radiopharmac

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“…This difference in the number of genes whose expression changed suggests that Selank acts not directly through the center of the specific binding of GABA, but rather allosterically by altering the affinity of the GABA receptor for GABA. Previously, it was shown that Selank is able to affect the specific binding of GABA to its own receptors, which may be caused by modulating properties of regulatory peptide, which apparently change the affinity of endogenous ligands under the influence of Selank on the receptor (V'Yunova et al, 2014 ). We can assume that the observed similarity of expression profiles of our study genes after administration of Selank and GABA partly confirms the hypothesis about the possible effect of the peptide through the regulation of the activity of GABA A receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, it was shown that in the presence of Selank the amount of the specifically bound ligand, [ 3 H] GABA, varied, and preliminary intranasal administration of peptide also induced changes in the number of specific binding sites of [ 3 H] GABA but did not affect the affinity of the receptors (V'Yunova et al, 2014 ). Based on these data, the authors suggested that Selank can lead to a rapid change in the state of the GABAergic system by binding the peptide to GABA receptors and, thus, allosterically modulating the activity of GABA A receptor.…”

Section: Introductionmentioning

confidence: 99%

Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission

et al. 2016

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Clinical studies have shown the similarity of the spectrum of physiological effects of Selank and classical benzodiazepines, such as diazepam and phenazepam. These data suggest that there is a similar basis of their mechanism of action. To test this hypothesis we studied the effect of Selank and GABA on the expression of genes involved in neurotransmission. We analyzed the expression of 84 genes involved in neurotransmission (e.g., major subunit of the GABA receptor, transporters, ion channels, dopamine, and serotonin receptors) in the frontal cortex of rats 1 and 3 h after the administration of Selank or GABA (300 μg/kg) using real-time PCR method. We found significant changes in the expression of 45 genes 1 h after the administration of the compounds. Three hours after Selank or GABA administration, 22 genes changed their expression. We found positive correlation between the changes in genes expression within 1 h after administration of Selank or GABA. Our results showed that Selank caused a number of alterations in the expression of genes involved in neurotransmission. The data obtained indicate that Selank is characterized by its complex effects on nerve cells, and one of its possible molecular mechanisms is associated with allosteric modulation of the GABAergic system.

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“…Clinical studies have shown that the anxiolytic effect of Selank is comparable to the effect of low doses of the benzodiazepine tranquilizers; however, the action of Selank is not accompanied by the characteristic side effects of those drugs [ 9 , 10 ]. Furthermore, Selank affects the specific binding of GABA to GABA A receptors, which may be caused by a change in affinity of endogenous ligand receptors under the action of Selank [ 11 ]. This suggests that the presence of Selank may change the action of classical BZD.…”

Section: Introductionmentioning

confidence: 99%

Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats

Kasian

Kolomin

Andreeva

et al. 2017

Behavioural Neurology

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It was shown that the anxiolytic effect of Selank is comparable to that of classical benzodiazepine drugs and that the basis of their mechanism of action may be similar. These data suggest that the presence of Selank may change the action of classical benzodiazepine drugs. To test this hypothesis, we evaluated the anxiolytic activity of Selank and diazepam in rats both under conditions of unpredictable chronic mild stress and in its absence, after the individual and combined administration of these compounds using the elevated plus maze test. We found that, even in the absence of chronic stress, the administration of a course of test substances changed anxiety indicators toward their deterioration, but the changes after the administration of a course of Selank were less pronounced. In conditions of chronic stress, anxiety indicator values after the simultaneous use of diazepam and Selank did not differ from the respective values observed before chronic stress exposure. The data obtained indicate that the individual administration of Selank was the most effective in reducing elevated levels of anxiety, induced by the administration of a course of test substances, whereas the combination of diazepam with Selank was the most effective in reducing anxiety in unpredictable chronic mild stress conditions.

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Peptide regulation of specific ligand-receptor interactions of GABA with the plasma membranes of nerve cells

Cited by 9 publications

References 32 publications

An integrated approach to study the molecular aspects of regulatory peptides biological mechanism

An integrated approach to study the molecular aspects of regulatory peptides biological mechanism

Selank Administration Affects the Expression of Some Genes Involved in GABAergic Neurotransmission

Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats

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