Effects of Inhibitors of Metabolism on Adenine Nucleotides and on 22Na and 42K and Net Movements in Rat Uteri at 25 °C

1971 ◽  
Vol 49 (3) ◽  
pp. 205-239 ◽  
Author(s):  
E. E. Daniel ◽  
Kathleen Robinson
Keyword(s):  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Atp Depletion ◽  
Atp Content ◽  
Sodium Efflux ◽  
Cellular Fraction ◽  
Glucose Depletion ◽  
Na Efflux ◽  
Per Se

The effects of 10−3 M iodoacetate (IAA) and (or) 10−3 M dinitrophenol (DNP) on Na and K fluxes and contents and on adenine nucleotide levels of isolated rat uterine horns were studied. Early 22Na efflux was slightly increased by DNP in the fresh and Na-rich tissues. IAA and DNP alone or together reduced 22Na efflux from the larger cellular fraction (No. 2) in both fresh and Na-rich tissues. 22Na efflux from the smaller cellular fraction (No. 3) was accelerated by IAA and by DNP in Na-rich tissues. DNP increased 22Na influx in both types of tissue and caused net Na gain and K loss. In fresh tissues IAA or IAA plus DNP accelerated 22Na influx, but slowed this influx in Na-rich tissues. In fresh tissues the ATP content was reduced by 50% by DNP. After a 60-min exposure with IAA and a 15- to 20-min exposure with IAA plus DNP, the ATP levels were negligible. The onsets of action of IAA or of IAA plus DNP on Na fluxes were correlated with ATP depletion, but early acceleration of 22Na efflux by DNP was not. In fresh tissues 42K influx was slightly decreased at the time of ATP depletion and the influx was further slowed as tissue potassium was replaced by sodium. IAA plus DNP increased K efflux in 10 min and IAA alone increased K efflux after 100 min. Thus K flux changes were not well correlated with ATP depletion. Substitution of K for all the sodium in the bathing media did not alter the quality of the effects of IAA or IAA plus DNP on sodium efflux. When prolonged glucose depletion eliminated ATP and ADP, the effects of IAA could not be duplicated. But IAA alone, or with DNP, still caused alterations in the 22Na efflux. Therefore IAA acted on ion fluxes by a mechanism other than ATP depletion. Both fresh and Na-rich tissues swelled after ATP depletion. An effect on internal osmotic pressure rather than ATP-depletion per se was postulated. Other studies showed that Na-rich tissues were resistant to shrinking by hypertonic sucrose and became more so secondarily after ATP depletion because of increased sucrose permeability. Evidence from studies of swelling, as well as flux data, suggested that at least two Na pumps were present. Both were ATP-dependent. One was ouabain-sensitive and exchanged Na for K, while the other was ouabain-insensitive and controlled movement of Na with water.

Effects of Inhibitors of Active Transport on 22Na and 42K Movements and on Nucleotide Levels in Rat Uteri at 25 °C

1971 ◽  
Vol 49 (3) ◽  
pp. 178-204 ◽  
Author(s):  
E. E. Daniel ◽  
Kathleen Robinson
Keyword(s):  
Water Content ◽  
Sodium Pump ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Compartment Model ◽  
Sodium Influx ◽  
Na Pump ◽  
Cellular Fraction ◽  
Na Efflux ◽  
External K

The effects of inhibitors of the sodium pump (K-free solution or ouabain) on Na and K fluxes, water content, and adenine nucleotides were studied in rat uterine horns. The same four-compartment model [Formula: see text] was applied to K efflux as to Na efflux. However, for K efflux the larger cellular fraction, C, contained 70% of tissue K, and D could usually be ignored. K-free solutions did not alter ATP, ADP, or AMP levels, and had only small effects on efflux of Na from fresh or Na-rich tissues. In these tissues ouabain decreased Na efflux from the faster, larger cellular fraction (BK2 ↓) without affecting adenine nucleotide levels. K-free solutions or ouabain increased sodium influx, but neither inhibitor caused swelling. The inhibitors decreased water content of fresh tissues and failed to interfere with extrusion of water accompanying Na from Na-rich tissues. In addition to the ouabain-sensitive pump, another Na pump insensitive to K levels or ouabain was postulated to be responsible for control of cell volume and part of Na efflux in uteri. The K efflux was increased by ouabain, but not by K-free solutions. The K influx was decreased by K-free solutions, but was not affected by ouabain. Increasing external K (concentrations of 18.4 mM and higher) did not diminish the effects of ouabain on Na or K efflux. Neither cocaine nor adrenaline prevented the effect of ouabain on the Na or K efflux or on the increased Na influx. No evidence was obtained that a Na exchange–diffusion system operated in K-free solutions. It was concluded that the accepted views about the operation of a Na pump involving (Na+ + K+)-activated, ouabain-sensitive ATPase have to be modified for rat uteri.

The Effect of Temperature on Sodium Movements in Rat Uteri and a Model for Control of their Ion Content

1971 ◽  
Vol 49 (3) ◽  
pp. 240-262 ◽  
Author(s):  
E. E. Daniel ◽  
Kathleen Robinson
Keyword(s):  
Atp Depletion ◽  
Rate Coefficients ◽  
Effect Of Temperature ◽  
Ion Content ◽  
Substantial Fraction ◽  
Cellular Fraction ◽  
Diffusion Controlled ◽  
Na Efflux ◽  
Pinocytotic Vesicles ◽  
Na Uptake

The uptake and efflux of 22Na was studied in isolated rat uterine horns (both fresh and Na-rich) at 5, 15, 25, and 37 °C. Reduction of temperature from 37 °C to 25 or to 15 °C reduced 22Na uptake into, and efflux from, both the extracellular space and cells to the degree expected of a diffusion-controlled process (Q10 < 2). Reduction of the temperature to 5 °C during uptake into Na-rich horns revealed that a substantial fraction of cellular sodium became less exchangeable. At 5 °C, 22Na efflux was also markedly reduced, more than from ouabain or ATP depletion. Analysis of this change by curve-peeling and by reducing the temperature at various stages of efflux suggested that the main cause was a shift of 22Na from the larger, faster cellular fraction (No. 2) to the slower cellular fraction (No. 3). Bound 22Na was also markedly increased. The rate coefficients from curve-peeling for both cellular fractions were decreased. Radioactivity still in fraction 2 at 5 °C emerged at a rate of about half that at 15 °C. However, an overall coefficient for efflux of 22Na which would have emerged in fraction 2 at 15 or 25 °C showed that the Q10 for 22Na efflux between 5 and 15 °C was about 15. Tissues did not swell when they gained sodium at 5 °C. The effects of ouabain to increase 22Na influx and 42K efflux were eliminated at 5 °C. The effects of ATP depletion by iodoacetate and dinitrophenol to decrease 22Na efflux and to increase 22Na uptake, K loss, and swelling were reduced at 5 °C. Prior ATP depletion altered but did not prevent the marked reduction of efflux by cooling to 5 °C. Efflux of lithium, but not of potassium, was markedly slowed at 5 °C. K-free solutions still increased 22Na uptake at 5 °C. A model involving pinocytotic vesicles to explain these and earlier results was postulated.

Strophanthidin-induced sodium efflux

1976 ◽  
Vol 194 (1115) ◽  
pp. 279-284 ◽  
Keyword(s):  
Absolute Magnitude ◽  
Monovalent Cations ◽  
Atp Content ◽  
Sodium Efflux ◽  
Na Efflux ◽  
The Absolute ◽  
Reversible Reduction ◽  
External Calcium

The external cation dependence of a strophanthidin-induced Na efflux in dialysed axons was examined. In the presence of strophanthidin the replacement of external Na with choline produced no appreciable changes in Na efflux, whereas the replacement of external Na with Mg brought about a large and reversible reduction. In the absence of external Ca the absolute magnitude of the reduction in Na efflux seen in Mg seawater was the same regardless of the ATP content of the axons; this reduction was similar to that observed in the presence of external calcium in low ATP axons. The present results, together with others already reported in the literature, suggest that the strophanthidin-induced Na efflux represents the outward component of an exchange of ions in which internal Na is exchanged for external monovalent cations.

The Energy Metabolism of Novikoff Ascites Hepatoma Cells. I. The Effects of Glucose on the Intracellular Level of Adenine Nucleotides

1971 ◽  
Vol 49 (6) ◽  
pp. 686-694 ◽  
Author(s):  
J. W. Gurd ◽  
P. G. Scholefield
Keyword(s):  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Rapid Decrease ◽  
Intracellular Level ◽  
Atp Content ◽  
Ascites Tumor ◽  
Ascites Hepatoma ◽  
Novikoff Hepatoma ◽  
Adenosine Phosphates ◽  
Layer Chromatography

When freshly prepared Novikoff hepatoma ascites tumor cells were incubated with glucose there was a rapid decrease in the ATP content of the cells. This was initially accompanied by an increased level of ADP but in the interval 6–10 min after the addition of glucose only 40% of the original adenine nucleotide content could be accounted for as adenosine phosphates. Analysis by thin-layer chromatography indicated breakdown via inosine 5′-phosphate (IMP), inosine, and hypoxanthine. Continued incubation led to resynthesis from hypoxanthine to IMP and thence to the adenine nucleotides.

scholarly journals The relation of sodium and potassium ion transport to the respiration and adenine nucleotide content of liver slices treated with inhibitors of respiration

1972 ◽  
Vol 129 (2) ◽  
pp. 427-438 ◽  
Author(s):  
G. D. V. Van Rossum
Keyword(s):  
Ion Transport ◽  
Concentration Ratio ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Critical Value ◽  
Endogenous Respiration ◽  
Atp Content ◽  
Nucleotide Content ◽  
Liver Slices ◽  
Potassium Ion Transport

1. The dependence of the net transport of Na+and K+by rat liver on the respiration has been determined by incubating slices in the presence of varying concentrations of respiratory inhibitors. 2. Neither the rate of net transport nor the total amount of each ion transported was inhibited unless the rate of endogenous respiration was decreased below a critical value of about 330mmol of O2/h per kg of protein (i.e. 50% of the total endogenous respiration). 3. The uninhibited rate of respiration could be varied over a twofold range (380–770mmol of O2/h per kg of protein) by the use of different substrates, but the critical value for the onset of transport inhibition was quite constant (290–360mmol/h per kg of protein) under these different conditions. 4. Slices incubated at 38°C without inhibitors showed an increase of their ATP content and the concentration ratio ATP/ADP. The final ATP content and concentration ratio, ATP/ADP, of slices treated with different concentrations of inhibitors were closely related to the rate of respiration. 5. The increased ATP content of the control slices during incubation was equal to the increase of total adenine nucleotides. At increasing degrees of respiratory inhibition the relative contributions of ADP and AMP to the total adenine nucleotide content increased. 6. The critical rate of respiration for the onset of inhibition of ion transport and the corresponding contents of adenine nucleotides provide estimates of the maximal values of certain parameters of energy metabolism required for the support of alkali-cation transport in the liver slices.

Mg2+ buffering in cultured chick ventricular myocytes: quantitation and modulation by Ca2+

1993 ◽  
Vol 264 (5) ◽  
pp. C1259-C1269 ◽  
Author(s):  
K. L. Koss ◽  
R. W. Putnam ◽  
R. D. Grubbs
Keyword(s):  
Cell Volume ◽  
Time Course ◽  
Ventricular Myocytes ◽  
Adenine Nucleotide ◽  
Atp Depletion ◽  
Atp Content ◽  
Fura 2 ◽  
The Difference ◽  
Adenine Nucleotide Pool ◽  
Mg Content

To characterize the Mg2+ buffering of cultured chick ventricular myocytes, cytosolic Mg2+ was increased by liberating Mg2+ normally chelated by ATP upon total depletion of ATP content. Because the total Mg content and cell volume remained constant during this time, the difference between the amount of Mg2+ liberated (2.7 mM) and the 0.9 mM increase in cytosolic Mg2+ activity measured fluorometrically with mag-fura-2 indicates a sizable Mg2+ buffering. A new term, the Mg2+ buffer coefficient (BMg), was derived to quantify this buffering. We also determined that cytosolic Mg2+ activity increased by only 0.6 mM in cells acutely exposed to zero external Ca2+ during ATP depletion. In the absence of extracellular Ca2+, the basal cytosolic Ca2+ activity (alpha Ca2+i) was reduced by 72%, whereas the increase in alpha Ca2+i induced by ATP depletion was substantially blunted; no difference in either the time course of adenine nucleotide changes or the Ca and Mg content was observed. The BMg value calculated for these cells indicates that Mg2+ buffering is substantially greater in the absence of extracellular Ca2+ (2.5) than when extracellular Ca2+ is present (1.4), indicating that alpha Ca2+i affects cytosolic Mg2+ activity in ventricular myocytes. Therefore the Mg2+ buffering of ventricular myocytes appears to be comprised of at least two components: 1) a Ca(2+)-insensitive adenine nucleotide pool and 2) a Ca(2+)-sensitive nonadenine nucleotide pool.

The Platelet of the Newborn Infant – Adenine Nucleotide Metabolism and Release

1980 ◽  
Vol 43 (02) ◽  
pp. 099-103 ◽  
Author(s):  
J M Whaun ◽  
P Lievaart ◽  
Keyword(s):  
Newborn Infant ◽  
Adenine Nucleotide ◽  
Platelet Rich Plasma ◽  
Adenine Nucleotides ◽  
Newborn Infants ◽  
Specific Radioactivity ◽  
Nucleotide Metabolism ◽  
Breakdown Product ◽  
Term Infants ◽  
Adenine Nucleotide Metabolism

SummaryBlood from normal full term infants, mothers and normal adults was collected in citrate. Citrated platelet-rich plasma was prelabelled with 3H-adenine and reacted with release inducers, collagen and adrenaline. Adenine nucleotide metabolism, total adenine nucleotide levels and changes in sizes of these pools were determined in platelets from these three groups of subjects.At rest, the platelet of the newborn infant, compared to that of the mother and normal adult, possessed similar amounts of adenosine triphosphate (ATP), 4.6 ± 0.2 (SD), 5.0 ± 1.1, 4.9 ± 0.6 µmoles ATP/1011 platelets respectively, and adenosine diphosphate (ADP), 2.4 ± 0.7, 2.8 ± 0.6, 3.0 ± 0.3 umoles ADP/1011 platelets respectively. However the marked elevation of specific radioactivity of ADP and ATP in these resting platelets indicated the platelet of the neonate has decreased adenine nucleotide stores.In addition to these decreased stores of adenine nucleotides, infant platelets showed significantly impaired release of ADP and ATP on exposure to collagen. The release of ADP in infants, mothers, and other adults was 0.9 ± 0.5 (SD), 1.5 ± 0.5, 1.5 ± 0.1 umoles/1011 platelets respectively; that of ATP was 0.6 ± 0.3, 1.0 ± 0.1,1.3 ± 0.2 µmoles/1011 platelets respectively. With collagen-induced release, platelets of newborn infants compared to those of other subjects showed only slight increased specific radioactivities of adenine nucleotides over basal levels. The content of metabolic hypoxanthine, a breakdown product of adenine nucleotides, increased in both platelets and plasma in all subjects studied.In contrast, with adrenaline as release inducer, the platelets of the newborn infant showed no adenine nucleotide release, no change in total ATP and level of radioactive hypoxanthine, and minimal change in total ADP. The reason for this decreased adrenaline reactivity of infant platelets compared to reactivity of adult platelets is unknown.Infant platelets may have different membranes, with resulting differences in regulation of cellular processes, or alternatively, may be refractory to catecholamines because of elevated levels of circulating catecholamines in the newborn period.

Modernization of Antimonopoly Policy in Russia (Economic Analysis of Proposed Changes in the Competition Law)

2005 ◽  
pp. 100-116
Author(s):  
S. Avdasheva ◽  
A. Shastitko
Keyword(s):  
Economic Analysis ◽  
Financial Markets ◽  
Financial Services ◽  
Competition Law ◽  
Commodity Markets ◽  
State Aid ◽  
Executive Power ◽  
Rule Of Reason ◽  
Per Se

The article is devoted to the analysis of the draft law "On Protection of Competition", which must substitute the laws "On Competition and Limitation of Monopolistic Activity on Commodity Markets" and "On Protection of Competition on the Financial Services Market". The innovations enhancing the quality of Russian competition law and new norms providing at least ambiguous effects on antimonopoly regulation are considered. The first group of positive measures includes unification of competition norms for commodity and financial markets, changes of criteria and the scale of control of economic concentrations, specification of conditions, where norms are applied "per se" and according to the "rule of reason", introduction of rules that can prevent the restriction of competition by the executive power. The interpretation of the "collective dominance" concept and certain rules devoted to antimonopoly control of state aid are in the second group of questionable steps.

scholarly journals L-Arginine Intake Effect on Adenine Nucleotide Metabolism in Rat Parenchymal and Reproductive Tissues

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
G. Kocic ◽  
J. Nikolic ◽  
T. Jevtovic-Stoimenov ◽  
D. Sokolovic ◽  
H. Kocic ◽  
...  
Keyword(s):  
Adenosine Deaminase ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Tissue Growth ◽  
Nucleotide Metabolism ◽  
Amp Deaminase ◽  
Male Impotence ◽  
Adenine Nucleotide Metabolism ◽  
Adenosine Concentration ◽  
Male Wistar Rats

L-arginine is conditionally essetcial amino acid, required for normal cell growth, protein synthesis, ammonia detoxification, tissue growth and general performance, proposed in the treatment of men sterility and prevention of male impotence. The aim of the present paper was to estimate the activity of the enzymes of adenine nucleotide metabolism:5′-nucleotidase (5′-NU), adenosine deaminase (ADA), AMP deaminase, and xanthine oxidase (XO), during dietary intake of L-arginine for a period of four weeks of male Wistar rats. Adenosine concentration in tissues is maintained by the relative activities of the adenosine-producing enzyme,5′-NU and the adenosine-degrading enzyme-ADA adenosine deaminase. Dietary L-arginine intake directed adenine nucleotide metabolism in liver, kidney, and testis tissue toward the activation of adenosine production, by increased5′-NU activity and decreased ADA activity. Stimulation of adenosine accumulation could be of importance in mediating arginine antiatherosclerotic, vasoactive, immunomodulatory, and antioxidant effects. Assuming that the XO activity reflects the rate of purine catabolism in the cell, while the activity of AMP deaminase is of importance in ATP regeneration, reduced activity of XO, together with the increased AMP-deaminase activity, may suggest that adenine nucleotides are presumably directed to the ATP regenerating process during dietary L-arginine intake.

Erythroid-Stimulating Agents in Cancer Therapy: Potential Dangers and Biologic Mechanisms

2009 ◽  
Vol 27 (25) ◽  
pp. 4217-4226 ◽  
Author(s):  
Brandon K. Hadland ◽  
Gregory D. Longmore
Keyword(s):  
Quality Of Life ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Detrimental Effect ◽  
Randomized Clinical Trials ◽  
Supportive Therapy ◽  
Endogenous Erythropoietin ◽  
Per Se ◽  
Erythropoietin Stimulating Agents

Erythropoietin-stimulating agents (ESAs) were originally designed to replace endogenous erythropoietin in patients with anemia secondary to renal failure. Their use has subsequently been expanded to include patients with anemia of other causes, including cancer patients, in whom deficiency of erythropoietin, per se, is not the primary cause of anemia. Although early studies showed promise of ESA administration in reducing the need for transfusions and improving the quality of life in cancer patients, several large randomized clinical trials have recently shown a potential detrimental effect of ESA administration on tumor progression and survival in these patients. These studies have called into question the safety of ESAs as supportive therapy in patients being treated for oncologic conditions. However, numerous questions remain to be addressed regarding the design of these studies, the effect of various targeted hemoglobin levels, and the potential biologic mechanisms proposed to explain promotion of tumor progression and reduced survival.

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