[Effect of water deprivation on serotonin metabolism in rat brain].
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Biomedical subjects
Publications and source records attributed to L N Ivanova.
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A significant increase in the water permeability was found in the rat outer medullary collecting duct (OMCD) cells in presence of 10-7M of vasopressin. The latter caused a decrease in the OMCD cell volume in isoosmotic medium in adult rats. In pups, the water permeability of the OMCD cells was very high. Vasopressin seems to be unable to decrease the cell volume of the OMCD cells in pups which suggests an immaturity of the cell transduction mechanism.
A significant amount of specific proteins are involved in kidney's response to vasopressin. A relative content of 120 kDa protein in the Wistar rat kidney medulla following a 3-day dehydration, was found to be 0.975 +/- 0.037 and after drinking 4% sucrose solution alone--0.871 +/- 0.038. The difference of protein 120 kDa content was not revealed in Brattleboro rats: in the control rats it was 0.814 +/- 0.044, and in the dehydrated ones--0.854 +/- 0.020. The findings suggest that vasopressin directly regulates the 120 kDa protein level in the kidney inner medulla.
Involvement of enzymes catabolizing hyaluronic acid (hyaluronidase, beta-glucuronidase, N-acetyl-beta-D-hexosaminidase) in the hydroosmotic action of vasopressin on the amphibian urinary bladder Rana Ridibunda was studied. It was found that vasopressin (50 nM), agonist of V2 receptors dDAVP (1.5 mcM) and forscolin (30 mcM) induce an activation of enzymes and its release into the Ringer solution at the mucosal surface simultaneously with the increase in the osmotic water flow. Maximal effect was observed 10 min later than hydroosmotic response. Release of enzymes under vasopressin effect was found in the absence of osmotic gradient and water flow through the epithelium. The repeated substitution of the outer Ringer solution for the fresh one resulted in the increase in the both the water permeability and the release of enzymes through the mucosal surface. We suggested that involvement of hyaluronate-hydrolases in the vasopressin effect is mediated by the cAMP-dependent mechanism. It is supposed that this effect creates conditions for the increase in the permeability of glycosaminoglycan structures covering adjacent to the apical cell surface.
Phosphorylation was shown to lead to a change in the conformational equilibrium toward E1 form associated with a decrease in apparent affinity for the K+ in alpha-1 subunit of the rat kidney Na+, K(+)-ATPase. Rate of transition from E2 to E1 was apparently unaffected by phosphorylation. ATP hydrolysis by the protein kinase C-phosphorylated Na+, K(+)-ATPase shows a decrease in the Vmax and Km for K+.
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Considerable differences were found in concentrations of specific vasopressin receptors and chromatographic profile of solubilised receptors of the rat and mouse kidneys. Development of sensitivity to vasopressin seems to be associated with an aggregated structure of the vasopressin receptor, alterations in the features of G-proteins in the cell membrane, and establishing of a functional connection between the receptor complexes and the G-proteins system.
Exposure of juvenile minks to artificial light conditions imitating early autumn (additional illumination from 20 June to 20 July followed by 8 h daylight from 21 July to 10 October--photoperiod I; 8 h daylight from 21 July to 10 October--photoperiod II) induced the prolonged modification of sex steroid concentrations. The increase in plasma testosterone concentrations during the prepubertal period was followed by a decrease before and during the mating period in experimental males. The concentration of oestradiol in plasma increased just before the start of the mating period (January and February) in females under photoperiod I, and these hormonal changes were accompanied by an increase in fertility. The conditions of photoperiod II (involving fewer hours of daylight) had less effect on the sex steroid concentration in the blood of females, and fertility was not changed. The response of gonads to hCG injection at the beginning of puberty (November) was higher in males exposed to photoperiod I conditions and in females exposed to both photoperiods than in control animals.
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Characteristics of G-proteins were studied in renal medulla of rats and mice of different ages. It was established that G-protein alpha-subunit gene expression has a specific dynamics with maximum on the 5-8-th day of life and at the end of weaning. It was shown that vasopressin does not stimulate G-protein GTPase activity in membrane preparations from immature kidneys. The differences of G-protein chromatographic characteristics were revealed. It is suggested that the development of vasopressin sensitivity of the kidney is related with the changes in G-protein system.
Serum corticosteroid-binding globulin (CBG) levels were measured in children (mean age 4 years) during heart surgery. Considerable decrease in CBG level occurred between baseline examination (416 +/- 39 nM) and the day of surgery (314 +/- 30 nM). Relatively simple closed heart surgery did not influence CBG level with maximal cortisol level being 20 +/- 4 micrograms/dl. Open heart surgery under conditions of profound hypothermia (26 C, without extracorporeal circulation) caused dramatic lowering of CBG level, particularly striking after resuscitation (180 +/- 20 nM). At the same time cortisol level reached extremely high values (78 +/- 8 micrograms/dl). These data suggest that CBG is likely to play an important role in pituitary-adrenal response to surgery under severe conditions of hypothermia and cardiac arrest.
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The effect of tactivin, a thymic hormonal factor, (MW 1-6 KD), on the adrenal glucocorticoid function in mice was studied. Tactivin (0.1-2 micrograms/mouse i.p.) produced a slight decrease in plasma corticosterone. The decrease was much more pronounced when tactivin was administered to mice with a high basal level of the hormone. The tactivin supplement had a significant suppressive effect on corticosterone production in both the whole adrenals and the intact isolated adrenal cells. When added at the doses of 0.00064-2 micrograms/ml to the isolated adrenal cells in the presence of ACTH, tactivin abolished the stimulatory effect of corticotropin on corticosterone production. The abolition was complete at a low dose (1.6 microIU/ml) and incomplete, yet significant, at a high dose of ACTH (1600 microIU/ml). The in vitro data are in a good agreement with those obtained in the in vivo experiments. The stimulatory effect of a synthetic analog of cAMP-Dibutyryl-cAMP on the steroidogenesis of adrenal cells was as pronounced as that of ACTH. Nevertheless, tactivin exerted no influence on Bu2-cAMP stimulation. The results indicate that tactivin prevents ACTH from acting on steroidogenesis at some time point preceding the formation of secondary messengers.
Polycardiography was used to examine myocardial contractile parameters: preejection and ejection periods and contractility coefficient in 90 patients with coronary heart disease running without complications postoperatively following aortocoronary bypass and cardiac aneurysm resection. The magnitude and length of lower myocardial contractility were found to be associated with the baseline extent of coronary and cardiosclerosis, the signs of congestive heart failure, the value of ejection fraction, and intraoperative parameters such as the duration of extracorporeal circulation and myocardial ischemia, the number of shunts and their blood flow. Early drug correction of complications and a scientifically substantiated approach to the physical rehabilitation of those operated on may be applied with due account of the changes in myocardial contractility.
Endogenous phosphorylation of proteins in cell suspensions of collecting tubes was studied. Using SDS disc electrophoresis in polyacrylamide gel with subsequent autoradiography, it was shown that vasopressin increases the 32P incorporation into two proteins with molecular masses of 15 kDa and 33 kDa, which serve as endogenous substrates for cAMP-dependent protein kinase. The hormone-dependent phosphorylation of these proteins was typical of the membrane fraction of collecting tube cells but was absent in the cytosolic fraction. The results obtained are suggestive of the direct involvement of vasopressin in the regulation of membrane protein phosphorylation by cAMP-dependent protein kinase which may increase the permeability of cells for H2O.
Specific binding of ADH by the membrane fraction of the kidney medulla was lower in the normal CBA mice than in mutant mice with nephrogenic diabetes. Gel filtration of the solubilized ADH receptors of mutants revealed the presence of an unidentified factor which caused cooperative binding of ADH. DEAE-chromatography revealed no difference between cytosolic cAMP receptors in normal and mutant animals. Assay of GTP-ase activity of the membrane fraction revealed that ADH increased this parameter in CBA mice but not in mutant animals. Cholera toxin significantly diminished membrane ATP-ase activity whereas membrane preparations from mutant mice developed a reactivity to ADH. GTP binding ability in these preparations was higher than inn intact ones. In CBA mice this ability increased dramatically. HPLC profiles of G-protein complexes with GNP were very different in CBA and mutant mice. Mutation seems to cause changes both in binding and in "cross-talk" link op-complex membrane receptor of ADH.