Biomedical subjects

L A Andreeva

Publications and source records attributed to L A Andreeva.

At least 19 recordsLinked to original sources

PubMed2007

Effects of corticoliberin CRF(4-6) fragment on pain sensitivity in rats.

The effects of the tripeptide fragment corticoliberin CRF(4-6) (Pro-Pro-Ile) on pain sensitivity were studied in rats using the hotplate method. CRF(4-6) given centrally (6, 30, and 150 nmol/rat) had dose-dependent antinociceptive actions: the latent period of the paw-licking response increased by 7.4 +/- 1.4, 10.1 +/- 1.5, and 16.7 +/- 4.2 sec from the control level of 10.2 +/- 0.9 sec. The durations of the effect were 30 min for CRF(4-6) at a dose of 6 nmol and 60 min for doses of 30 and 150 nmol of tripeptide. Administration of the corticoliberin antagonist alpha h CRF(9-41) (centrally, 6.5 nmol) 60 min before tripeptide completely blocked the antinociceptive effects of CRF(4-6) (6 nmol). Thus, corticoliberin receptors are involved in mediating the antinociceptive influence of CRF(4-6). It can be suggested that the tripeptide either directly interacts with corticoliberin receptors or modulates the activity of CRFergic neurons.

Animals↗

PubMed2006

Degradation of the ACTH(4-10) analog Semax in the presence of rat basal forebrain cell cultures and plasma membranes.

Here a new approach of the elucidation of paths of proteolytic biodegradation of physiologically active peptides, based on the use of a peptide with isotopic label at all amino acid residues and the enrichment of HPLC samples with unlabeled peptide fragments in UV-detectable concentration, has been proposed. The method has been applied for the investigation of degradation dynamics of the neuroactive heptapeptide MEHFPGP (Semax) in the presence of plasma membranes, and cultures of glial and neuronal cells obtained from the rat basal forebrain. The splitting away of ME and GP, and formation of pentapeptides are the predominant processes in the presence of all tested objects, whereas the difference in patterns of resulting peptide products for glial and neuronal cells has been detected. In conclusion, the approach applied allows analyzing physiologically active peptide concentrations in biological tissues and degradation pathways of peptides in the presence of targets of their action.

Adrenocorticotropic Hormone↗

PubMed2006

Effects of semax against the background of dopaminergic receptor blockade with haloperidol.

We studied the neurotropic effects of ACTH(4-10) analog semax against the background of dopaminergic receptors blockade with haloperidol. Intranasal administration of semax (0.05, 0.2, and 0.6 mg/kg) produced virtually no effect on disturbances of orientation and exploratory reactions and motor activity caused by intraperitoneal injection of 0.2 mg/kg haloperidol. By contrast, preliminary administration of 0.05 mg/kg semax prevented haloperidol-induced disturbances in active avoidance conditioning.

Administration, Intranasal↗

PubMed2006

Effects of corticoliberin fragment CRF(4-6) on sexual behavior in male rats [corrected].

Centrally administered doses of the tripeptide corticoliberin fragment CRF(4-6) (Pro-Pro-Ile) suppressed mating behavior in male rats. Doses of 1 and 2 microg of the tripeptide produced dose-dependent increases in the latent periods of mounting, intromission, and ejaculation. Changes in measures of sexual behavior demonstrated that the corticoliberin fragment CRF(4-6) suppressed both sexual motivation and sexual performance.

Animals↗

PubMed2006

[Protective effect of peptide semax the rat heart in acute myocardial infarction].

Semax, a member of ACTH-derived peptides family, has been employed in the treatment of acute ischemic stroke in patients. It decreased neurological deficit and reduced NO hyperproduction in the rat brain, caused by acute cerebral hypoperfusion. We suggested that semax is also able to protect rat heart from ischemic damage in acute myocardial infaction (AMI). AMI was induced by left coronary artery occlusion, myocardial ischemic area averaged 30 % of left ventricle. In 2 hours after coronary occlusion, the AMI group developed 11 % reduced mean arterial blood pressure and 48 % increased diastolic blood pressure in left ventricle in comparison with sham-operated control group. However, infusion of either dobutamine, which directly stimulates myocardial contractility, or sodium nitroprusside and phenylephrine, that change vascular resistance and thus cardiac afterload, did not reveal distinctions in hemodynamic parameters between groups. These data indicate absense or only moderate cardiac dysfunction in rats with AMI and are consistent wih morphometrical and histochemical studies that did not detect any necrotic or apoptotic (TUNEL-test) changes in left ventricular cardiomyocytes in spite of development of distinct ischemic disturbances of mitochondria and nuclear in about 50 % of cardiomyocytes in 2 hours after AMI. Semax (150 microg/kg), given i. p. 15 min and 2 hours after coronary occlusion, caused no effect on cardiac function, but completely prevented ischemia-induced ultrastructural changes of cardiomyocytes. This protective effect was accompanied by the ability of peptide to blunt the increase in plasma concentrations of nitrates, observed in AMI group.

Adrenocorticotropic Hormone↗

PubMed2005

Seasonal effects of Selank on the behavior of hibernating animals.

We studied the seasonal effects of peptide preparation Selank on orientation and exploratory activity in 36 arctic ground squirrels Citellus undulatus in the open-field and hole-board tests. Selank most significantly increased behavioral activity of hibernating animals in the spring and fall. The test peptide had no effect on locomotor activity of animals. The selective stimulatory effect of Selank on exploratory behavior of hibernating animals was season-dependent. The maximum effect was observed under conditions of seasonal depression-like state.

Animals↗

PubMed2005

Natural and hybrid ("chimeric") stable regulatory glyproline peptides.

The present concept of relative instability of regulatory peptides (RPs) in organisms must be amended. The recently characterized family of glyprolines and some other prolyl-glycyl-proline (PGP)-containing oligopeptides show the stability quite comparable with those of major pharmacological preparations. The ability of glyprolines to pass gastro-enteric tract barriers opens ways to per-oral administration of this new group of drugs such as semax, selank and their fragments. The most interesting approach is the creation of hybrid ("chimeric") peptide drugs combining the unmodified representatives of various natural RPs that distinctly manifest their inherent physiological activities and cooperate with each other in stabilization of whole peptide in vivo. As the result, the activity of such peptides as semax and selank may have value in a vide variety of pathological processes.

Journal Article↗

PubMed2005

[Effect of the corticoliberin fragment CRF(4-6) on blood pressure and heart rate in rats].

The effects of tripeptide corticoliberin fragment CRF(4-6) (Pro-Pro-Ile) on blood pressure and heart rate of rats were investigated. Intracerebroventricularly injected CRF(4-6) (1.5-15.0 nmol/head) increases the mean arterial pressure and heart rate in conscious and anaesthetized animals in a dose-dependent manner. Corticotropin releasing factor antagonist: alpha-helical CRF(9-41) (6.5 nmol) completely abolished the influence of tripeptide CRF(4-6) (1.5 nmol) on blood pressure and heart rate in anaesthetized rats. This result indicates that corticoliberin receptors are involved in cardiovascular effects of CRF(4-6).

Animals↗

PubMed2005

[Influence of acute and chronic administrations of beta-casomorphins on the maternal motivation in albino rats].

The influence of food-derived opioid peptides beta-casomorphines on the manifestation of nursing albino rats maternal behavior was investigated. It was shown that both acute and chronic (during the postnatal period) administration of beta-casomorphin-7 (Tyr-Pro-Phe-Pro-Gly-Pro), the typical representative of this group of peptides, decreases the level of the parental motivation. The effects of beta-casomorphin-7 were naloxone-dependent; N-terminal-reduced analogues had a significantly lesser activity. The obtained results testify in favor of the probable role of casein opioid fragments which were formed in mammary glands of a nursing female, in the development of maternal behavior abnormalities. At the same time, beta-casomorphins could be considered as the limiting factors to the excessive manifestation of the parental motivation.

Animals↗

PubMed2005

[Dependence of long-lasting effects of the ACTH(4-10) analogue semax on the time of its neonatal administration].

Long-lasting behavioural effects of chronic administration of synthetic ACT(4-10) analogue Semax (MEHFPGP) during early neonatal life were studied. The peptide was injected daily intraperitoneally in dose 0.05 mg/kg during the first, second or second-third weeks of postnatal development. It was shown that the peptide injections during the first week lead to a decrease and during second or second-third weeks--to an increase of exploratory activity in 4-8-week aged rats. Furthermore, the peptide adminictration at all times diminished anxiety and improved learning ability of adult rats. The data obtained show that Semax neonatal administration during the first three weeks of life modulates development of brain structures involved in regulation of exploration, anxiety and learning.

Adrenocorticotropic Hormone↗

PubMed2005

[Influence of corticotropin-releasing factor fragment CRF(4-6) on male rat sexual behaviour].

Centrally administered corticotrophin-releasing factor fragment CRF(4-6) (Pro-Pro-Ile) inhibits components of male rat sexual behaviour. Administration of 1 and 2 microg of tripeptide leads to dose-dependent increase in mount, intromission and ejaculation latencies. Alterations of sexual behaviour parameters suggest suppression of both sexual motivation and sexual performance.

Animals↗

PubMed2005

[Effect of corticoliberin fragment CRF(4-6) on pain sensitivity in rats].

The effects of corticoliberin fragment CRF(4-6) (Pro-Pro-Ile) on pain sensitivity of rats in "hot plate" test were investigated. Intracerebroventricular administration of tripeptide CRF(4-6) (6, 30, 150 nmol/head) induced dose-dependent antinociception: the latency of paw lick response increased by 7.4 +/- 1.4, 10.1 +/- 1.5 and 16.7 +/- 4.2 s respectively from the basic level of 10.2 +/- 0.9 s. Duration of tripeptide antinociceptive action was 30 min (for 6 nmol) and 60 min (for 30 and 150 nmol). Pretreatment with corticotropin-releasing factor antagonist alpha-helical CRF(9-41) (6.5 nmol/head) 60 minutes before tripeptide administration completely abolished the antinociceptive effects of CRF(4-6) (6 nmol). Therefore corticoliberin receptors seem to be involved in realization of tripeptide influence on pain sensitivity. The data obtained suggest that CRF(4-6) can either directly interact with corticoliberin receptors or modulate activity of CRF-ergic neurons.

Animals↗

PubMed2004

The neuroprotective effects of Semax in conditions of MPTP-induced lesions of the brain dopaminergic system.

This report describes studies cf the effects of the ACTH(4-10) analog Semax (MEHFPGP) on the behavior of white rats with lesions to the brain dopaminergic system induced by the neurotoxin MPTP. Neurotoxin was given as single i.p. doses of 25 mg/kg. Neurotoxin injections were shown to decrease movement activity and increase anxiety in the animals. Daily intranasal administration of Semax at a dose of 0.2 mg/kg decreased the severity of MPTP-induced behavioral disturbances. The protective activity of Semax in MPTP-induced lesions of the brain dopaminergic system may be associated with both its modulating effect on the dopaminergic system and the neurotrophic action of the peptide.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed2003

In vitro and in vivo opioid activity of [DPro(6)]dermorphin, a new dermorphin analogue.

To study the effects of inducing stereo-chemical modifications in the structure of dermorphin (DM) so as to improve its mu-opioid receptor affinity and its resistance to C-terminal enzymatic degradation, in the Institute of Molecular Genetics of Moscow, we synthesized a new DM analogue ([DPro(6)]DM) and analyzed the changes induced in the biological activities of DM by substituting the Pro(6) residue with DPro(6). We compared the activity of the new DM analogue and DM in in vitro assays and in in vivo tests of analgesia, thermoregulation, heart rate recordings, and gastrointestinal motility in rats. In the in vitro tests, guinea pig ileum (GPI) and mouse vas deferens (MVD), although the opioid activities of [DPro(6)]DM indicated that the peptide was always less potent than DM, its lower IC(50) ratios (mu/delta) showed that it had higher mu-opioid receptor selectivity. In the in vivo analgesic test, [DPro(6)]DM, when injected intraperitoneally (i.p.) (0.5-5 and 10mg/kg) in rats, had the same antinociceptive efficacy as DM and when injected intranasally (i.n.) (0.005 and 0.02 mg/kg) it induced a more stable and long-lasting analgesia than DM (the AUC was about 91% higher for [DPro(6)]DM than for DM). Moreover, these data confirm that the intranasal route is advantageous for peripheral drug administration. In the heart rate study, [DPro(6)]DM and DM (0.5mg/kg, i.p.), induced a similar, weak bradycardia. The only difference was that [DPro(6)]DM induced a longer-lasting effect than DM. Conversely, in body temperature regulation [DPro(6)]DM induced weaker inhibitory activity than DM (56% of the DM-induced response); it did so only in a cold environment and at the maximal used dose (0.5mg/kg, i.p.) without inducing vasomotor effects. In the gastrointestinal study, [DPro(6)]DM and DM (0.005, 0.05, and 0.5mg/kg, i.p.) significantly slowed upper gastrointestinal transit of a charcoal meal and inhibited colonic propulsion. Comparison of the ED(50) values of [DPro(6)]DM (0.03 mg/kg) and DM (0.009 mg/kg) showed that the DM analogue was about three times less potent than DM in slowing gastrointestinal and colonic transit. In conclusion, all these data overall suggest that structural maneuvering in the Pro(6)-residue of the DM molecule changes its affinity for mu-opioid receptor subtypes and confirms the usefulness of experimental studies involving structural modifications in obtaining new therapeutic agents.

Analgesics, Opioid↗

PubMed2003

Consequences of progestational hypoxia in pregnant rats and its peptide correction (EEG data).

We studied immediate and delayed changes in ECG in female albino rats subjected to acute hypobaric hypoxia on days 4-5 of pregnancy and evaluated the possibility of correction of hypoxia-produced disturbances with some peptides. Acute hypoxia lengthened the mean RR interval, increased heart rate variability, and decreased the monotony index. Hypoxia induced considerable changes in the structure of ECG that reflected the development of arrhythmias and conduction disturbances. These changes in ECG persisted during the posthypoxic period. Intranasal administration of heptapeptides Semax and beta-casomorphin-7 to pregnant females promoted recovery from acute hypoxia and normalized ECG in the posthypoxic period.

Adrenocorticotropic Hormone↗

PubMed2003

Effect of acute progestational hypoxia on the content of biogenic amines in the brain of albino rat pups: Peptide correction.

We studied the effect of exposure to acute hypobaric hypoxia in the progestational period on the content of biogenic amines in the brainstem and cerebral cortex in rat pups of different age. The possibility of correcting hypoxia-induced changes with regulatory peptides was evaluated. We found that early antenatal hypoxia disturbs maturation of catecholaminergic systems in the brain. It should be emphasized that the differences from the control varied depending on the age of rat pups. Single intranasal administration of Semax heptapeptides and beta-casomorphine-7 to pregnant females prevented changes in the content of biogenic amines in CNS of the offspring during postnatal ontogeny.

Aging↗

PubMed2003

[Effect of a corticoliberin (CRF4-6) on the rat heart rate and behavior].

The effects of tripeptide corticoliberin fragment CRF4-6 (Pro-Pro-Ile) on heart rate and behaviour of rats with simultaneous monitoring of these parameters in free-moving animals in their home cage were investigated. Intracerebroventriculary administered CRF4-6 (6, 30, 150 nmol) induces arousal effect increasing the duration of active behaviour, decreasing the duration of passive behaviour and sleep both. At the same time the tripeptide increases the heart rate during sleep, passive and exploratory activity. CRF4-6 (30, 150 nmol) also increases the heart rate in anaesthetised rats. All observed effects of the tripeptide are dose dependent. Taking into account these facts we suggest that CRF4-6 influences behaviour and heart activities independently.

Animals↗

PubMed2002

[Neuroprotective effects of semax in MPTP-induced disturbances of brain dopamine system].

Effects of an ACTH (4-10) analogue Semax (MEHFPGP) on behaviour of white rats with MPTP-induced disturbances of brain DA-system have been studied. It was shown that MPTP administration (25 mg/kg) reduced motor activity and auhmented the anxiety level in rats. Semax administration (daily intranasal 0.2 mg/kg) attenuated behaviour disturbances induced by neurotoxin. The observed protective action of Semax in rats with MFTP-induced DA system disturbances may be due to both its modulating influence on the brain DA system and peptide neuroprotective effects.

Administration, Intranasal↗