Serum Activity of Proteolytic Enzyme Trypsin in Rats under Conditions of Water and Food Deprivation.

Trypsin is mainly regarded as a digestive enzyme, but there is evidence that activation of protease-activated receptor-2 (PAR-2) leads to behavioral changes. There are no data on trypsin activity in the serum of animals under conditions of thirst and starvation in the available literature. In our experiments, water deprivation led to a significant (p⩽0.05) increase in trypsin activity in rats, and food deprivation led to its decrease in comparison with controls (free access to water and food). After deprived rats received water and food, a decrease in trypsin activity was observed in both experimental groups. Changes in trypsin activity under conditions of water or food deprivation and after satiation were accompanied by shifts in some biochemical parameters of the bloods. Under conditions of metabolic stress (starvation and thirst), opposite changes in trypsin activity seem to indicate its participation in the mechanisms of adequate restructuring of metabolism and maintenance of vital processes in the body.

LOCAL RENIN-ANGIOTENSIN SYSTEM OF SMALL INTESTINE.

The renin-angiotensin system (RAS) is the universal multiple-factor regulator of many vital processes at the organismal, tissue and cellular levels. Classical (circulating) RAS provides maintenance of arterial pressure, a water and salt balance, lipid and glucose homeostasis. Local tissue RAS are functioning independently and participating in metabolic processes and protective reactions. Local RAS of a small intestine mucosa is presented practically by a complete rangeof the components (renin, angiotensinogen, angiotensin-converting enzymes, angiotensin receptors) localized, mainly, in an intestinal epithehum, lamina propria and muscularis mucosa. Local RAS participates in regulation of the most levels of activity ofa small intestine, influencing on an intestinal motility, secretory-transport processes, adaptation and protective reactions. The experimental data presented in this review are very promising for the detection of possible complications when using drugs that alter the activity of the RAS-related unexplored effects of the interaction of these drugs with their potential targets, localized not only in the blood vessels, but also directly to the niucosa of the gastrointestinal tract. This is especially important in connection with the extensive use of drugs that modulate the activity of the RAS in the practice of the treatment of cardiovascular diseases such as hypertension, atherosclerosis, endothelial dysfunction, and others.

Behavioral and Hemodynamic Effects of Free and Protein-Bound Angiotensin IV in Rats in Experimental Hypo- and Hyperglycemia: Comparative Aspects.

In rats with acute hypo- and hyperglycemia the initial effects of free angiotensin IV and its complexes with functionally different carrier proteins (transport protein BSA, neuron-specific protein S100b) on hemodynamics and behavior of rats were qualitatively altered, in comparison with those in intact animals. At the same time, free angiotensin IV under conditions of hypo- and hyperglycemia paradoxically acquired functions of angiotensin II (moderate hypertension, tachycardia, polydipsia and activation of instrumental drinking behavior). Concurrently, complexes of angiotensin IV with BSA and S100b acquired functions of free angiotensin IV (hypotensia, suppression of drinking behavior). It is suggested that complexes of angiotensin IV with functionally different proteins are involved in a differentiated way first in compensation of behavior and hemodynamics impairment produced by acute and/or chronic hypo- and hyperglycemia, and then in qualitative transformation of these adaptive processes into stable pathological condition involving mechanisms of so called "metabolic memory".

Comparative study of the effects of free bound and carrier protein angiotensin II in experimental hypoglycemia and hyperglycemia.

Experimental hypoglycemia and hyperglycemia eliminated the differences in the regulatory functions of free angiotensin II and its complexes with carrier proteins (transport protein BSA and neurospecific protein S100b) in rats. Under these conditions, free and protein-bound angiotensin II primarily suppressed operant drinking behavior and reduced the hypertensive and tachyarrhythmic effects in comparison with control rats. These changes were most pronounced during acute hyperglycemia. We hypothesized that complexes of angiotensin II with functionally different proteins are differentially and simultaneously involved in not only compensation of behavioral and hemodynamic disturbances during acute and/or chronic hypoglycemia and hyperglycemia, but also their transformation into pathological processes mediated by the so-called metabolic memory mechanisms.

[Estimation of atherogenic immune complexes containing modified lipoproteins in complement fixation tests].

A method for determining atherogenicity of the immune complexes containing multiple modified low-density lipoprotein (mmLDL) in complement fixation test has been found. In the proposed method, the precipitate immune complexes containing mmLDL (IC mmLDL) was prepared from human serum by treating it with buffer (8.3% of th PEG 3350 and 3.3% PVP 12600 th in the ratio 1: 1.2) for 10 min at 23 °C. IC mmLDL aggregates were separated by centrifugation at 3100g for 10 min at 23 °C. The precipitate IC mmLDL was dissolved in buffer without PEG and PVP, cholesterol content and the degree of binding of guinea pig complement were measured. Atherogenicity of the IC mmLDL was registered as the ratio of the degree of complement binding to cholesterol in the the immune complexes.

Free and protein-bound angiotensin II(1-7)in the regulation of drinking behavior and hemodynamics in rats.

We compared physiological activity of synthetic analogues of endogenous protein-peptide compounds, complexes of angiotensin II(1-7)with functionally different proteins (transport protein, serum albumin; and neurospecific Ca(2+)-binding protein, S100b). Physiological activity of angiotensin II(1-7)was shown to depend on the type of a carrier protein. Our results suggest that complexes of angiotensins with BSA and S100b are strong factors for the integration of central and peripheral functions at the homeostatic and behavioral level.

Modification of normal activities of angiotensin II and angiotensin IV in rats with experimental hypo- and hyperglycemia.

Changes in blood glucose levels are paralleled by modification of normal activities of angiotensin II and angiotensin IV. Hypo- and hyperglycemia similarly reduced the hypertensive effect of angiotensin II and similarly distorted the initial hypotensive effect of angiotensin IV. Presumably, the adaptation and compensatory processes in the renin-angiotensin system under conditions of shifted homeostatic constants manifest by phenomena of external reintegration and redistribution of functions of its individual peptide components. This provides restructuring of the mechanisms of intra- and intersystemic organization of physiological functions under extreme conditions.

[Immune links in the system organization of behaviour].

The work is devoted to the research of immune mechanisms in self-control of various functional systems of homeostatic and behavioral levels. Distinction of immune mechanisms in rats with different prognostic stress-resistance is established. Immunization of rats by conjugates of various neuromediators with bovine serum albumin selectively changes the animals stress-resistance. Participation cytokines in reactions of a brain's separate neurons and their interaction with a leading neuromediator - norepinephrine is established. Individual changes of pro- and anti-inflammatory cytokines in blood serum are shown in rats with different stress-resistance. There are revealed features of morphological distinctions of immunogenic structures small intestine fabrics in animals with various behavioral activity in the "Open field" test.

Complexes of angiotensin IV with functionally different proteins in the regulation of drinking behavior and hemodynamics in rats.

We compared physiological activity of synthetic complexes from angiotensin IV and functionally different proteins (transport protein, bovine serum albumin; and neurospecific Ca(2+)-binding protein, S100b) as model analogues of endogenous protein-peptide complexes. Physiological activity of angiotensin IV was specifically modified by these proteins. Our results suggest that complexes of angiotensin IV with bovine serum albumin and S100b are strong factors for the integration of central and peripheral functions at the homeostatic and behavioral level.

Physiological effects of complexes of angiotensins with functionally different carrier proteins.

We compared activity of synthetic complexes of angiotensin II and functionally different proteins (transport protein, serum albumin and neurospecific Ca2+-binding protein S100b) as analogues of endogenous protein-peptide complexes. Physiological activity of angiotensin II was specifically modified by these proteins. It was hypothesized that the complex of angiotensin II and S100b is primarily involved in the regulation of hemodynamics, whereas the complex of angiotensin II and bovine serum albumin plays a role in the formation and realization of drinking behavior.

[Regulatory peptides in system mechanisms of goal-directed behavior: experience of physiological activity study].

The paper presents some new data and original approaches to study of the role of opioid and vasoactive peptides in the integrative functioning of the brain. The authors performed a comparative analysis of the physiological activity of native and complex (combined with protein) forms of these biologically active substances, and discuss a possible role of autoimmune processes in peptide self-regulation of goal-directed behavior.

Protein-peptide complexes of angiotensins in the mechanisms of thirst motivation.

A comparative analysis of the physiological actions of native angiotensin I and angiotensin II and protein-peptide complexes of angiotensin I and angiotensin II on drinking behavior in rats was performed. The protein-peptide complexes of angiotensin I and angiotensin II had wider spectra of physiological activity than the native peptides. Protein-conjugated angiotensin I, unlike the motivationally neutral native angiotensin I, produced marked activation of innate drinking behavior in mice. The protein-peptide complex of angiotensin II showed selective effects on acquired drinking behavior. These data are assessed with respect to the specific involvement of protein-peptide complexes of angiotensin I and angiotensin II in the mechanisms of thirst motivation during the performance of innate and acquired habits.

[Peptide-protein complexes of angiotensins in the mechanisms of thirst]. / Belkovo-peptidnye kompleksy angiotenzinov v mekhanizmakh motivatsii zhazhdy.

The comparative analysis of learned and natural drinking behavior under native angiotensin-I (A-I), angiotensin-II (A-II) and its protein-peptides complexes (PPC) administration in rats, was performed. Various effects of these substances on drinking behavior were observed. PPC of A-I became a dipsogenic agent as compared with the native one. Moreover, PPC of A-II facilitated selectively learned and not natural forms of drinking behavior. It's suggested that PPC of angiotensins play a specific role in endogenous mechanisms of thirst. An important function of this complexes due to their conformational properties and participation in realization of basic needs, is discussed.

[Protein-peptide complexes in the mechanisms of inborn and learned behavior patterns]. / Belkovo-peptidnye kompleksy v mekhanizmakh vrozhdennykh i priobretennykh form povedeniia.

Protein-peptide complexes involved in learned and natural drinking behavioral patterns were comparatively analyzed in rats. Active immunization with protein-conjugated angiotensin II and beta-endorphin produces some behavioral responses. It is suggested that protein complexes of these peptides play a specific informational role in the systemic organization of learned behavior. The paper discusses whether these complexes perform an important function due to their conformational properties and their participation in the hierarchical organization of integrative processes in the nervous system.

[Conjugated forms of angiotensin II and beta-endorphin in systemic organization of goal-oriented behavior]. / Kon''iugirovannye formy angiotenzina II i beta-éndorfina v sistemnoi organizatsii tselenapravlennogo povedeniia.

The effects of conjugated angiotensin II and beta-endorphin on the rat drinking behavior that was natural and formed due to preliminary learning were comparatively analyzed. Some behavioral responses were also studied after active immunization with the above agents. It is suggested that the conjugated forms of the regulatory peptides play a specific informational role in the systemic organization of goal-oriented behavior. These substances due to their conformational properties and involvement in the hierarchic organization of integrative processes in the nervous system are shown to be of great value.

[The effect of a preparation from the horns of the saiga antelope on the goal-directed drinking behavior of rats]. / Vliianie preparata iz rogov antilopy saigi na tselenapravlennoe pit'evoe povedenie krys.

Saitarin (an extract from the horns of antelope Saiga) depresses complex instrumental drinking behavior of rats and induced specific changes in the structure of goal-directed behavioral acts. Such changes are to a certain extent suppressed by naloxone. The obtained evidence suggest that the effects of saitarin are caused by its predominant influence on the processes of reinforcement in the course of realization by animals of the learned behavioral acts.

[An attempt at the objective evaluation of systems quanta in the drinking behavior of rats]. / Opyt ob''ektivnoi otsenki sistemokvantov pit'evogo povedeniia krys.

The system architectonics of "systemoquanta" of rat drinking behavior was objectively evaluated in the dynamic process of its formation by means of studying intermediate and final results. The developed experimental equipment made it possible to determine characteristic features of formation and realization of drinking "systemoquanta" and the dynamics of their internal structure. Various "strategies" of system organization of identical behavior were revealed in rats of different groups. The revealed peculiarities of the internal structure of "systemoquanta" in rats of different groups are probably determined by the innate individual differences in the processes of prediction and estimation of intermediate and final results in the framework of strategic "systemoquantum" of drinking behavior.

[A comparative analysis of the complex realization of the goal-directed behavior of animals under chronic morphine and cocaine administration]. / Sravnitel'nyi analiz realizatsii slozhnogo tselenapravlennogo povedeniia zhivotnykh pri khronicheskom vvedenii morfina i kokaina.

A new approach to estimation and prediction of morphine and cocaine effects was proposed based on the analysis of animal behaviour directed to a satisfaction of one of the main biological needs, thirst. Both morphine and cocaine did not essentially effect the level of the basic biological (drinking) motivation by the index of the general volume of liquid consumption. Both drugs produced opposite effects on the duration of recognition/manipulation and drinking components of the structure of water-reinforced instrumental act. The proposed methodology is of diagnostic and prognostic value in respect of the complex behavioural effects of the drugs and presumably some other active factors.