[Natriuretic effect of exenatide: high efficacy and site of action].

Exenatide injection to female Wistar rats induced an increase in diuresis, urinary sodium and mild potassium excretion. The maximum natriuretic effect of exenatide was 18500 times more pronounced compared to that of furosemide in equimolar dose. The natriuretic and diuretic effects after combined administration of maximum doses of exenatide and furosemide were additive, which was indicative of different mechanisms of their action on the nephron. Exenatide probably inhibits sodium reabsorption in renal proximal segment. The data obtained might be essential for assessment of the clinical use of exenatide to excrete extracellular fluid excess in cases of edemation and to maintain potassium balance.

[K+/Na+ in the animal extracellular fluid at weathering of granitoids and problem of the origin of life].

Leaching of granitoids of the paleoproterozoic age was performed from several seconds to 360 days in water solutions (pH < 6.0) in the oxygen or argon medium. Under these conditions the entrance of K+ into the solution has been shown to occur at the higher rate than that of Na+. The obtained data are considered as evidence in favor of a possibility of the existence at the earlier stages of the Earth geologic history of water reservoirs with predominance of K+ over Na+. The K+/Na+ ratio exceeding 1 has been shown in prokaryotes, in cells and tissues of the free living and parasitic species of invertebrate and vertebrate animals. At the same time in the extracellular fluid of the fresh water, marine, and terrestrial animals, in which the Na+ concentration varies from 13 to 482 mmol/l, the K+/Na+ ratio is preserved at the level of 0.034 +/- 0.001. These results are discussed in connection with the problem of origin of protocells and of concentration ratios of monovalent cations in water phases of multicellular organisms.

[Synthesis and investigation of effects of conopressin S analogues on ion and water excretion by rat kidney].

The investigation deals with effect of analogues of conopressin S--a peptide of the vasopressin family with amino acid replacement in the 2nd and 4th positions (characteristic of invertebrate peptides)--on transport of water and ions in the rat kidney. At administration to female Wistar rats, 1-deamino-conopressin S produced a weak action on water transport and had no effect on urinary K+ and Na+ excretion. Its analogue, 1-deamino-Tyr2-conopressin S, caused antidiuretic and kaliuretic action without affecting the Na+ excretion. Estimation of significance of the variant of optic isomer of arginine in the 4th and 8th position of the molecular for the antidiuretic and kaliuretic action of the peptide showed that 1-deamino-Tyr2,D-Arg4-conopressin S and 1-deamino-Tyr2,D-Arg4,8-conopressin S did not affect the urinary K+ excretion and renal water reabsorption, whereas action of 1-deamino-Tyr2,D-Arg8-conopressin S did not differ from action of 1-deamino-Tyr2-conopressin S. Thus, it has been established that the selective kaliuretic action of analogues of conopressin S on rat kidney depends on the presence of tyrosine in the 2nd and of L-arginine, but not of D-arginine, in the 4th position of the molecule.

[Quantum processes in evolution of regulation of living system (mathematical modelling)].

We have developed an imitation model of the appearance of regulation of physiological functions of protocell at the initial stages of evolution of living system. It is based on suggestion of the appearance of signal function in spontaneously formed products of partial hydrolysis of the protocell polypeptides, based on which there appear the regulatory molecules--quanta of regulation. For construction of the model, the mathematical apparatus of final automats and of genetic algorithm is used. The model has demonstrated the positive role of involvement of regulatory peptides in the system of regulation of protocell functions to provide its viability under the changing envelopment conditions.

[Comparison of reabsorption of osmotically free water in the bud and energy of interaction of vasotocin analogs with a V2-receptor].

The calculated values of the binding energy of nonapeptides with receptors in docking with their influence on reabsorption of osmotically free water in a rat bud in vivo were compared. Vasotocin and some its analogs were intramuscularly introduced to non-narcotized rat females of the Wistar line in doses from 0.1 pmol to 0.5 nmol/kg of body weight against the background of peroral water load (50 ml/kg of body weight). A significant correlation between the calculated interaction energy of peptides with V2-receptors and an increase of reabsorption of osmotically free water in the rat bud stimulated by injection of nonapeptides was found. The results evidence that alterations in rat bud in vivo caused by analogs of vasotocin and their interactions with V2-receptors can be accurately simulated.

[S.S. Yudin. To the 120th anniversary of birth].

In October, 2011 120 years from the birth day of the great surgeon acad. USSR Ac. Med. Sci. S.S. Judin. Article include data on S.S.Judin's work and his life in Novosibirsk, new materials of the biography of the great surgeon, original photos.

[Incretory function of the kidney].

Participation of kidney in maintenance of constancy of parameters of the organism internal medium is connected with formation in it of physiologically active substances. They are components of systems of regulation of water-salt balance, arterial pressure, blood coagulation, erythropoiesis. Mechanisms of normalization by kidney of concentration of hormones in blood and of modulation of action of hormones are analyzed.

[Similarity of natriuretic action and qualitative differences of the hydrouretic action of 1-deamino-arginine-vasotocin and furosemide in rats].

Injections of furosemide at a dose of 0.3 micromol per 100 g body weight or 1-deamino-arginine-vasotocin (1dAVT) at a dose of 0.05 nmol per 100 g body weight induced nearly equal increase in urinary sodium excretion: up to 406 +/- 20 and 405 +/- 23 micromol/2 h, respectively. Increase in urinary sodium excretion after injection of 1d-AVT was followed by enhancement of solute free water reabsorption from -0.51 +/- 0.05 to -2.75 +/- 0.11 ml/2 h (p < 0.05). On the contrary, furosemide injection induced a significant decrease in solute free water reabsorption to -0.19 +/- 0.06 ml/2 h (p < 0.05) and led to the appearance of solute free water in urine during peak of diuretic reaction. These data for the first time show that furosemide not only decreases sodium reabsorption, but also blocks some componentin molecular mechanism of vasopressin-dependent increase of the osmotic permeability of water.

[Influence of new neurohypophyseal hormone analogs on sodium and water reabsorption in rat kidney].

New analogs of some neurohypophyseal hormones (oxypressin, hydrin, glumitocin, vasotocin) have been synthesized. Experiments with injection of these peptides to rats showed that substitution of C-terminal glycinamide on beta-ethanolamine (glycinol) or ethylamine in 1-deamino-arginine vasotocin resulted in loss of natriuretic but not antidiuretic activity. Analogs of oxypressin and hydrin exhibited neither natriuretic activity nor ability to affect water reabsorption. Glumitocin analog induced renal sodium ion excretion and did not influence potassium ion excretion.

[Principles of organization and evolution of systems of regulation of functions].

Evolution of living organisms is closely connected with evolution of structure of the system of regulations and its mechanisms. The functional ground of regulations is chemical signalization. As early as in unicellular organisms there is a set of signal mechanisms providing their life activity and orientation in space and time. Subsequent evolution of ways of chemical signalization followed the way of development of ways of delivery of chemical signal and development of mechanisms of its regulation. The mechanisms of chemical regulation of the signal interaction is discussed by the example of the specialized system of transduction of signal from neuron to neuron, of effect of hormone on the epithelial cell and modulation of this effect. These mechanisms are considered as the most important ways of the fine and precise adaptation of chemical signalization underlying functioning of physiological systems and organs of the living organism.

[Diabetes mellitus: renal osmoregulating function].

AIM: To evaluate the kidney status from osmotic urine concentration in different stages of diabetes mellitus (DM) to define whether not only glomeruli and proximal tubules, but also renal medullary substance structures are involved into the pathological process, as well as their reaction to endogenous vasopressin production. SUBJECTS AND METHODS: Forty patients with a 1-to-28-year history of DM, including 18 with diabetic nephropathy, 10 with chronic renal failure, and 22 without diabetic nephropathy, were examined. Urine and blood osmolality were determined and renal osmoregulating function was estimated. RESULTS: Decreased glomerular filtration rate was found in relation to the duration of DM. The osmolality of nocturnal urine samples tended to diminish during short-term deprivation depending on the duration of DM. Increased diuresis in DM was shown to correlate with the higher reabsorption of osmotically free water. CONCLUSION: Diminished renal concentrating capacity in DM appears to depend on evolving renal failure rather than vasopressin resistance. The application of a new approach, by calculating the clearance of sodium-free water, suggests that its increased reabsorption favors normalization of serum osmolality in hyperglycemia.

[Human physiology: kidney].

The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

[Determination of ion content and localization of vasopressin and aquaporin receptors in the gerbil kidney after the flight aboard biosatellite "Foton M3"].

After 12 days on space fight, body mass of gerbils decreased by 32.9%; however, the effective systems of regulation did not let changes in the concentration of Na, K, Mg ions in fresh samples of the renal cortex. These data are viewed as a reflection of the regulation systems strategy to preserve the optimal conditions for functioning of the kidney, a vital body organ. The cations were reduced significantly in the renal medulla when calculated for dry mass and compared with the synchronous control. This could have changed the osmoregulating function of the kidney during space fight and, due to small cations accumulation, caused the drop of the cortex/medulla osmotic gradient. Locations of V1a-, V1b- and V2-receptors and aquaporin 1 and 2 in renal tubule cells of gerbils before and fight are described.

[Physiology, biomedicine, medicine].

The physiology throughout centuries was considered as the basic fundamental science in medicine. Rapid development of molecular biology, genetics and of some other natural sciences in 2nd half XX demanded century not only the answer to a question on the sciences defining the base of development of medicine, but also key problems of its progress. The biomedicine is formed, its methods are discussed, is frequent in system of natural sciences, parities with physiology. The special attention is given unconditional necessity of finding-out of molecular mechanisms of functions, targets of action of physiologically active substances and obligatory correlation of data of modeling with the same processes in conditions in vivo in whole body. The role of various sciences in the decision of fundamental problems of medicine, a place and role of physiology in modern medicine is shown.

[Effects of vasotocin analogs on excretion of Na+, K+, and Mg2+ ions via rat kidney].

Experiments on rats showed that the intramuscular injections of arginine-vasotocin (AVT), 1-deamino-arginine-vasotocin (1dAVT) or 1-deamino-1-monocarba-arginine-vasotocin (1dlmcAVT) at a dose of 5 x 10(-11) mole per 100 g body weight increase renal excretion of Na+, K+, and Mg2+. Antagonist of V1 receptors (OPC-21268) decreases the effect of 1dAVT nonapeptides on renal excretion of the studied ions. A model of VIb-receptor is constructed and a correlation is shown between the energy of interaction of the V1b-receptor and the natriuretic effect of the studied vasotocin analogs.

[Imitational modeling of evolution: from organic macromolecules to protocell and animal cell].

A dynamic imitational model is developed of initial stages of cell evolution based on role of environmental cation concentration. The model is developed on our hypothesis, concerning the medium of the appearance of protocells. Could be potassium water reservoirs rather than sea salt water with its predominance of sodium salts. The necessary elements of appearance the protocells served organic molecules, code of their synthesis, and formation of macromolecules under favorable ion concentration in environment High K+ and Mg2+ concentration and bow Na+. The model is based on an assumption that one of the first stages in evolution of life was the appearance in potassium-magnesium water reservoirs of organic molecules capable for selfreplication on the basis of genetic code and formation of protocells with potassium cytoplasm. The model has demonstrated necessity of formation of cell envelope for development of the protocell. Replacement of the dominant cation in water reservoirs-potassium by sodium-required the appearance of ion-transporting devices in plasma membrane and their participation in adaptation of cells to environment. This stage of evolution was accompanied by the most important morpho-functional event--formation of the plasma membrane instead of cell envelope. The membrane provided the ion asymmetry in the cell (preservation of K+ in it) relatively to the sodium external medium for maintaining optimal intracellular medium. In the model system, predecessors of animal cells elaborated mechanism of maintenance of the potassium cytoplasm with the sodium counter-ion dominating in the environment.

[Evolutionary physiology by the data of publications of 1965-2005].

Evolutionary physiology as independent direction of physiology was formed in the XX century and was rapidly developing in its second half. To evaluate some tendencies of this process, we analyzed publications in Journal of Evolutionary Biochemistry and Physiology, one of the leading specialized periodicals on this problem. Analysis of works published for 4 decades has shown that the majority of papers deals with study of evolution of function of the nervous system (40-60 papers per year), less papers concern study of functions of sensory and visceral systems (20-30 per year). Among the used method, the most widely spread is the comparative-physiological method. By the end of the 1990s the number of works with use of methods of embryophysiology decreased. In the performed studies, predominant are physiological methods. Use of biochemical methods decreased, while of methods of molecular biology increased. The most often used objects of studies were mammals. By the end of the XX--beginning of the XXI century, in the greater number of papers the object of study has become human, while the number of publications in which experiments were performed on amphibians, reptiles, and birds decreased. More than a half of all works were carried out in St. Petersburg (Leningrad); the number of papers submitted from Moscow institutions gradually decreased, but the number of works from regions of Russia rose. Most studies were performed at institutes of the Russian Academy of Sciences and universities, while the number of papers from institutes of the Russian Academy of Medical Sciences decreased. For the last few years, several generalizations on evolution of functions and functional evolution have been formulated; handbooks and monographs on problems of evolutional physiology have been published.

[Coupled evolution of digestive, respiratory, circulatory, and excretory systems: a model investigation].

A model is developed of evolution of an organism with digestive, respiratory, circulatory, and excretory systems at the single system. The model is realized on the basis of the language STELLA 8.0. A balance is found between perfection of each individual physiological system and necessary energy expenditures for survival of the organism as a whole. The model is based on a coupled development of several visceral systems. There is analyzed effect of a change of consumption of substances with food and of oxygen amount on their oxidation, a branching of blood flow to organs, specifically to kidneys, to excrete final products of metabolism from blood. The energy expenditures for circulation are believed to be proportional to blood flow in a given organ. An increase of efficiency of renal excretion from blood of final metabolic products and toxic substances has a favorable effect on inner medium and activity of each cell of an individual, but increases of the organism energy expenditures. Interrelation of these factors under conditions of adaptation to changing environmental conditions determines peculiarities of evolution of each physiological system in an individual.

[Dynamics of absorption of yellow fluorescent protein in intestine and reabsorption in kidney in rat postnatal ontogenesis].

In experiments of the 5, 12 and 25-day old rat pups and adult rats in has been shown that after administration of yellow fluorescent protein (YFP) into stomach, its partial absorption in the non-degraded state in the small intestine takes place, with subsequent transport to kidney with blood flow and accumulation in cells of the proximal nephron segment. With age of rats, intensity of the intestinal YFP absorption decrease; the YFP accumulation in the kidney is more active in rats of the younger age groups than in adult animals. No accumulation of YFP in liver was revealed. The obtained data indicate an intensive absorption of YFP in the non-hydrolyzed form in the rat pup small intestine in early postnatal ontogenesis and an important role of kidney in protein metabolism and in proteolysis of exogenous proteins.