Behavioral effects of original tetrapeptide, an analog of N-terminal nociceptin fragment.

The study examined the effect of an analog to N-terminal nociceptin fragment AcOH×Phe-Gly-Gly-Phe-NH(2) on the behavior of albino rats. This tetrapeptide (5 µg/kg intraperitoneally) significantly enhanced motor and exploratory activity in mature rats and in 42-day pups and produced opposite effects in 21-day rat pups, which attests to the complex dynamics of maturation of nervous structures involved in the realization of nociceptin action.

[Myelopeptide MP-5 and fluorescent derivatives: synthesis and biological activity].

The Val-Val-Tyr-Pro-Asp bone marrow peptide (MP-5) and an analogue (MP-5-Lys) were synthesized. Fluorescent derivatives, Ftc-MP-5 and MP-5-Lys(Ftc), were prepared. The biological activity of MP-5 and MP-5-Lys was studied in vitro and in vivo. The MP-5 peptide caused 60-84% inhibition of growth of the following mouse cancers: lymphatic leukemia P-388, melanoma B-16, and cervical carcinoma CUC-5. These peptides also restored functional activity of T lymphocytes that was inhibited by metabolic products of the HL-60 leukemic cell line. MP-5-Lys(Ftc) was shown to preserve the functional properties of MP-5 toward T lymphocytes, but Ftc-MP-5 was practically inactive.

[The pharmacological modulation of group behavior and biorhythms in the dynamics of a chronic experiment]. / Farmakologicheskaia moduliatsiia gruppovogo povedeniia i bioritmov v dinamike khronicheskogo éksperimenta.

Cyclic daily experiments were conducted using the standard method of free behavior of animals in an "open field" (Opto-Varimex, USA) with by the hour recording of locomotor parameters. The neuromodulating activity of 124 pharmacological agents was compared according to the size and duration of their stimulating or depressant effect.

Localization of a fibrin polymerization site complementary to Gly-His-Arg sequence.

Dansyl-labeled tetrapeptide Gly-His-Arg-Pro which mimics the central fibrin polymerization site was used to investigate its binding to a number of fibrinogen fragments containing different numbers of domains. The tetrapeptide was found to bind to fragments DH(95 kDa), DL(82 kDa) and DY(63 kDa) but not to the TSD(28 kDa) fragment. The DY fragment differs from the TSD by the presence of beta and beta C domains. Therefore these domains, which are formed by the C-terminal part of the beta chain, possess a polymerization site complementary to the Gly-His-Arg containing counterpart.

[The immunostimulating properties of cholecystokinin octapeptide and its fragments]. / Immunostimuliruiushchie svoistva oktapeptida kholetsistokinina i ego fragmentov.

Immunostimulating properties of cholecystokinin octapeptide (CCK-8) were evaluated in experiments on adult normal and thymectomized mice, in vitro. It was shown that CCK-8 stimulates IgM-PFC production to SRBC, but does not change the immune response to Vi-antigen. CCK-8 increases the number of Thy-I+ spleen T cells and restores thymus-dependent immune response in thymectomized mice. CCK-8 has no effect on neutrophil phagocytosis activity in vitro. The immunostimulating activity of CCK-8 is related mainly to C-terminal fragment (identical to pentagastrin tetrapeptide) since the N-terminal CCK-8 tetrapeptide displays negligible effect in all tests.

[The hypnogenic effects of delta sleep-inducing peptide (DSIP) analogs: a comparative study in rabbits and rats]. / Gipnogennye éffekty analogov del'ta-sonindutsiruiushchego peptida (DSIP): sravnitel'noe izuchenie u krolikov i krys.

Hypnogenic effects of 3 DSIP analogs with a higher stability against aminopeptidase activity have been studied in rabbits and rats using intraventricular administration (injections and infusions). An analog (D-Ala-2) DSIP augmented slow wave and paradoxical sleep within the 5th, 8th and 11th hours of the recording period. An analog (D-Val-2) DSIP made the same within the 8th and 10th hours, and hexapeptide (D-Ala-2) DSIP (1-6) increased sleep during the 1st, 3rd, and 5th hours. Both nonapeptides augmented sleep in rabbits as well as in rats, though hexapeptide produced this effect in rabbits only, that might be related to some difference in distribution and colocalization of endogenous DSIP-like peptide in the pituitary of two rodent species. It may be suggested that hypnogenic activity of DSIP analogs is determined by the structure of administrated molecule, being mediated by such hormones as GRF and CLIP.

[The effect of regulatory peptides on water absorption in the large intestine of the frog]. / Vliianie reguliatornykh peptidov na vsasyvanie vody v tolstoi kishke liagushki.

Preparation of isolated large intestine of the frog was filled with Ringer's solution diluted with distilled water (1:5) and was placed into the glass with normal Ringer's solution. The preparation was weighed within every 30 min and the osmotic permeability was determined for water of the mucous and serous layers of the intestine. Then one of the peptides was added to Ringer's solution and the experiment continued. It is stated that bombesin, neurotensin, encephalins, substance P, somatostatin, pituitrin are able to change liquid absorption from the large intestine cavity when the concentration of Ringer's solution in the cavity and from its serous surface is the same. Bombesin and neurotensin inhibited while encephalins stimulated liquid absorption and these effects depended on the transport of ions. Liquid absorption by the osmotic gradient decreased using bombesin, substance P and increased using somatostatin. More complex peptide-peptide relations are observed if using pituitrin and other peptides. cAMP is shown to participate in bombesin effects.

[The effect of tuftsin on fibrin polymerization in vitro and on the hemostatic system when administered intravenously to healthy animals]. / Vliianie taftsina na polimerizatsiiu fibrina in vitro i sistemu gemostaza pri vnutrivennom vvedenii zdorovym zhivotnym.

Taftsine tetrapeptide has antiprocoagulatory properties in vitro in the presence of plasma. Taftsine exerts depolymerization influence on fibrin monomer in concentrations of 10(-1) to 10(-9) mg/ml. At intravenous injection in doses of 1 mg and 300 ug/kg, taftsine causes the increase in plasma clotting time and significant increase in enzymatic and nonenzymatic fibrinolysis. The effect can be observed during 120 min after injection of the peptide.

[Minor peptides of animal proteins as antibiotics and possible factors of nonspecific immunity]. / Malye peptidy belkov zhivotnykh kak antibiotiki i vozmozhnye faktory nespetsificheskogo immuniteta.

Screening of more than twenty short synthetic peptides characteristic of different proteins has revealed antimicrobial activity of the KRFAE peptide--from human preproenkephalin A against gram-negative bacteria. Modification of the peptide structure by means of administration of d-amino acids has permitted obtaining dKRFdLE analogue with the expressed and stable antimicrobial activity in vitro when growing bacteria on the minimum glucose-mineral medium. Changes and rearrangements of aminoacids in the dKRFdLE peptide in the second, third and fourth positions sharply decreased anti-microbial activity. The weaker antimicrobial activity as compared with that in dKRFdLE was peculiar to peptides with the other primary structure. Possible participation of peptides as antibiotics in the mechanisms of nonspecific immunity as well as the methods of their rational search are discussed.

[Analysis of new opiate-like peptides using a radioreceptor method]. / Analiz novykh opiatopodobnykh peptidov radioretseptornym metodom.

A screening of new synthetic opioid-like peptides has been carried out by the radioreceptor assay using selective labeled ligands to mu-, delta- and gamma-opioid receptors of the rat brain membranes. With this aim peptides from sequences of the following proteins were used: kapporphin-Tyr-Ser-Phe-Gly-Gly and its analogues-Tyr-Ser-Phe-Gly-Gly-NH2, Tyr-D-Ser-Phe-Gly-Gly, Tyr-D-Ser-Phe-Gly-Gly-NH2, myelorphin-Phe-Gly-Tyr-Gly-Gly, interenkephalin B-Arg-Arg-Gln-Phe-Lys and chimeric peptide IEPhBin 1-Tyr-Gly-Gly-Phe-Leu-Arg-Pro-Tyr-Ile-Leu consisting of leu-enkephalin and pentaneurotensin. It has been found that myelorphin has a prevalent affinity to mu-receptor, while the kapporphin analogues both to mu- and delta-receptors. The presence of pentaneurotensin in chimeric peptide does not affect the specificity of binding to opioid receptors, but decreases affinity to mu- and delta-receptors approximately by an order as compared to leu-enkephalin. Kapprorphin and interenkephalin B displace neither of the selective labeled opioid ligands under study.

[The hormonal sensitivity of a transplantable adenocarcinoma of the large intestine]. / Gormonochuvstvitel'nost' perevivnoi adenokartsinomy tolstoi kishki.

It was found that repeated transplantation of ACATOL strain cells resulted in a loss of their sensitivity to growth-stimulating effect of pentagastrin. The effect of gastrin receptor antagonist proglumide, on ACATOL cells growth was inconstant. ACATOL tumor was sensitive to VIP and glucagon in vitro (as shown by adenylate cyclase activity assay), that makes the model promising for selecting potent hormone drugs against colorectal cancer.