На препаратах изолированного сердца крысы при регистрации механической активности, а также на препаратах изолированных предсердий при регистрации потенциалов действия показано ингибиторное действие АДФ-рибозы. Показано, что эффекты АДФ-рибозы являются самостоятельными и не связаны с действием ее метаболитов. Ингибиторные эффекты опосредуются А1 аденозиновыми рецепторами. На фоне блокирования А1-рецепторов, АДФ-рибоза вызывает развитие положительного хронотропного эффекта в изолированном сердце. Данный эффект может быть обусловлен активацией АДФ-рибозой А2 аденозиновых рецепторов.

The inhibitor of monoaminooxydase isatin and the ligand of B-receptors cholecystokinin-4 play a significant role in the suppression and induction of depressive and anxiety states. We induced the formation of auto-antibodies to these compounds against their conjugates with antigen-carrier by immunization of white rats. The result was long-term (more than 2 months) stimulation of depressive and anxiety behavior after immunization to isatin and, in contrast, the suppression of such behavior after immunization to cholecystokinin. The perspective of immunochemical approach to long-term correction of behavior is discussed.

The effects of antimicrobial proteins of neutrophils [human defensins (HNP), rabbit defensins (NP) and human lactoferrin (LF)] on platelet aggregation and cytoplasmic free Ca2+ levels ([Ca2+]i) have been studied. The results show that HNP (0.1 to 40.0 mu g/ml) or NP (0.1 to 100.0 mu g/ml) were unable to trigger platelet aggregation and [Ca2+]i change. However, HNP (40.0 mu g/ml) reduced thrombin, collagen and ADP-induced aggregation of washed platelets as well as the [Ca2+]i increase caused by thrombin, ADP and LPS. NP inhibited [Ca2+]i increase in ADP- or LPS-stimuiated platelets too. Nevertheless, it was not accompanied by a reduction of platelet aggregation. LF in the concentration range from 0.1 mu g/ml to 100.0 mu g/ml did not influence the platelet activation induced by thrombin, ADP, collagen or LPS. Participation of if in the regulation of platelet activity was observed only with a high concentration (200.0 mu g/ml) of protein and was expressed as a (Ca2+]i increase. These data show that defensins and if participate in neutrophil-mediated modulation of platelet functional activity.

Yersinia pseudotuberculosis, Brucella abortus, andFrancisella tularensis strains producing a recombinant β-endorphin have been obtained. The highest production of this peptide, which displays physiological activity, was recorded for cells of theY. pseudotuberculosis strain 2243 (pSK95E).

The effect of the total fraction of human defensins (HNP-1, HNP-2, and HNP-3) on the cytoplasmic Ca2+ content ([Ca2+]i) in the platelets of healthy donors was studied. At concentrations of 0.1–40 μg/ml and an incubation time of 10 min defensins have no effect on [Ca2+]i in platelets labeled with Fura-2AM. However, at higher concentrations (100 μg/ml) they increased platelet [Ca2+]i. In addition, defensins (40 μg/ml) inhibited the Ca2+ increase in platelets induced by thrombin, adenosine diphosphate, and the lipopolysaccharide ofS. typhimurium endotoxin. The most pronounced inhibitory effect was observed in a suspension of thrombin-stimulated platelets. It is shown that the effect of human defensins on the functional activity of platelets is due to the alterations in the intracellular Ca2+.

The effects of human neutrophil peptide defensin were studied on human platelet function. Defensin (0.1-40 micrograms/mL) did not promote platelet aggregation. Defensin decreased platelet aggregation responses to ADF, collagen or thrombin. Defensin significantly lessened ATP level, released during platelet aggregation, and malondialdehyde production, induced by thrombin and collagen. These data reveal that defensins involve in cell-cell interaction between platelets and neutrophils counteracting agonist-induced platelet activation.

It has been shown, that vaccine strain of tularemia microbe, F.T.ISE., which produced recombinant beta-endorphin, when administered to CBA mice. It was shown to increase in the threshold level of pain sensitivity and is associated with peptides associated changes the stereotypic behavior. The observed correlated in time with the pattern of the dynamics of culture in the experimental animals and were associated with the level of recombinant beta-endorphin synthesis.

The effects of defensin, a peptide derived from human neutrophils, on aggregation of human peripheral blood monocytes were studied. Defensin (0.01 microgram/mL--100 micrograms/mL) caused a distinct dose dependent aggregation of normal donor monocytes. In addition, defensin increased the rate of monocyte aggregation induced by arachidonic acid or phorbol myristate acetate. Additional doses of defensin added to monocytes preactivated by this peptide produced no further aggregation. These data suggest that human defensin is an important physiological mediator released by neutrophils to regulate functions of monocytes.