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 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.

[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.

[Highly active analogs of opiate-like peptides historphin and kapporphin]. / Vysokoaktivnye analogi opiatopodobnykh peptidov gistorfina i kapporfina.

Analgetic activity of analogues of new opioid peptides historphine Tyr-Gly-Phe-Gly-Gly and capporphine Tyr-Ser-Phe-Gly-Gly was studied. Analogues of historphine Tyr-D-Ala-Phe-Gly-Gly and of capporphine Tyr-D-Ser-Phe-Gly-Gly exceeded 10(3)-fold the Leu-encephaline efficiency using a tail-jerk test and their derivatives containing amide group in the C-end position--10(4)-fold. All the four analogues increased the resistance period in the heat plate test. Naloxone removed or decreased the effect of these peptides studied. After repeated administration peptides Tyr-D-Ala-Phe-Gly-Gly-NH2 and Tyr-D-Ser-Phe-Gly-NH2 were similar in the activity to the most strong native opioid peptide desmorphine. Considering that analogues of historphine and capporphine exhibited high analgetic activity, they may be used as promising structures in more complicated modifications in order to produce highly effective analogues of opioid peptides.

[Opiate-like peptides with primary structure different from that of enkephalins]. / Printsipial'no otlichnye po pervichnoi strukture ot énkefalinov opiatopodobnye peptidy.

Some new opiate-like peptides originating from opioid peptide precursors, dinorphine, histone H2b, major myeline protein, natriuretic atriopeptide and from the immunomodulating protein splenin whose primary structure differs essentially from that of enkephalins are described. Being intracysternally injected to mice, all the peptides under study caused a naloxone-sensitive analgetic effect as could be judged from the tail pinch tests. The effects of some opiate-like peptides were much stronger than that of leu-enkephalin. According to their primary structure, the opiate-like peptides can randomly be allocated into two families. Dipeptide Lys-Arg and free arginine also possess a marked analgetic activity which is abolished by naloxone. It seems likely that the epiate-like activity of the peptides under study is due to the similarity of their secondary and ternary structure to that of enkephalins of to their involvement in the regulation of opioid peptide metabolism.

[The role of complementary E2 and D2 centers in the reaction between fibrin and fibrinogen]. / Rol' komplementarnykh tsentrov E2 i D2 v reaktsii mezhdu fibrinom i fibrinogenom.

The effect of fibrinogen on the two steps of polymerization of two fibrin forms differing in the set of polymerization sites (fibrin-desAA and fibrin-desAABB) was studied. It was shown that fibrinogen inhibited the protofibril growth and fibril formation at the stage of lateral aggregation more effectively with fibrin-desAABB than with fibrin desAA. When the fibrinogen D2-site was blocked by tetrapeptide Gly-His-Arg-Pro, the key structure of the E2-site, the inhibitory activity of fibrinogen diminished. A conclusion is drawn that the high susceptibility of fibrin-desAABB to fibrinogen is due to the interaction of the E2-active site with the D2-site of the fibrinogen molecule. The concentration dependence of the tetrapeptide Gly-His-Arg-Pro-induced inactivation of fibrinogen and the effects of temperature and Ca2+ on the tetrapeptide interaction with fibrinogen were investigated.

[Spike activity of neurons of the ventromedial hypothalamus of the rabbit in response to cholecystokinin application to the cornea]. / Impul'snaia aktivnost' neironov ventromedial'nogo gipotalamusa krolika pri applikatsii na rogovitsu glaza kholetsistokinina.

Microapplication to the rabbit eye cornea of the [Glu26] analogue of nonsulphated C-terminal octapeptide cholecystokinin reduced 2-5-fold the firing rate of the ventromedial hypothalamus neurons whereas [Glu26, 32] induced a 2-3-fold increase of the firing rate. Contralateral application increased 1.2-2.3-fold the latencies of responses. Nonsulphated C-terminal octapeptide cholecystokinin, its analogue [Glu32] and 0.9% NaCl solution exerted no obvious effect.

[Effect of natural neurotensin and its analog on gastric secretion and levels of various peptides in dog blood]. / Vliianie prirodnogo neirotenzina i ego analoga na sekretsiiu zheludkai soderzhanie nekotorykh peptidov v krovi sobak.

I.v. administration of neurotensin and its analogue DTch1I--neurotensin considerably decreased stomach secretion induced with pentagastrin but did not suppress stomach secretion induced with histamine, neither a microapplication of 10 micrograms in 3 microliter of neurotensin affected the secretion whereas the dose 50 micrograms in 3 microliter decreased both volume and acidity of the juice. I.v. administration of neurozensin increased the gastrin, neurotensin and the substance P contents in the dog blood. Microapplication of neurotensin to the globus pallidus with simultaneous i.v. administration of histamine increased the level of the serum gastrin.