Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Agonist occupancy of the cloned human serotonin (5-HT)1A receptor expressed in HeLa cells stimulates Na+/K+ ATPase activity as assessed by rubidium uptake. The purpose of the study was to determine which of the receptor-associated signaling mechanisms was responsible for this effect. 5-HT stimulated Na+/K+ ATPase 38% at 2 mM extracellular potassium, an effect characterized by a decrease in apparent K0.5 from 2.8 +/- 0.3 to 1.8 +/- 0.3 mM potassium without a significant change in apparent Vmax. The EC50 for the transport effect was approximately 3 microM 5-HT. The response was pertussis toxin-sensitive but did not involve inhibition of adenylate cyclase, as stimulation of Na+/K+ ATPase by 5-HT was observed in the presence of excess dibutyryl cAMP. Protein kinase C was not required for the response since short-term incubation with the phorbol esters phorbol 12 myristate, 13 acetate (PMA) and phorbol 12,13-dibutyrate (PDBu) did not mimic the 5-HT effect. Moreover, 5-HT increased Na+/K+ ATPase activity after inactivation of protein kinase C by overnight incubation with PMA. 5-HT and the sesquiterpene lactone thapsigargin increased cytosolic calcium in this cell model, and the EC50 for 5-HT corresponded with that for stimulation of Na+/K+ ATPase. Both thapsigargin and A23187, a calcium ionophore, also increased Na+/K+ ATPase activity in a dose-responsive fashion. The response to 5-HT, thapsigargin, and A23187 was blocked by conditions that removed the cytosolic calcium response. By two-dimensional gel electrophoresis, we established evidence for a calcium-sensitive but protein kinase C-independent signaling pathway. We conclude that the 5-HT1A receptor, which we have previously shown to stimulate phosphate uptake via protein kinase C, stimulates Na+/K+ ATPase via a calcium-dependent mechanism. This provides evidence for regulation of two separate transport processes by a single receptor subtype via different signaling mechanisms.
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PMID:Short-term regulation of Na+/K+ adenosine triphosphatase by recombinant human serotonin 5-HT1A receptor expressed in HeLa cells. 217 7

Previous studies showed that ouabain-sensitive rubidium (86Rb+) uptake by rabbit lung epithelial cells increases at birth, followed by a more gradual postnatal increase, reaching adult values by age 30 days. To see whether these changes in ouabain-sensitive cation transport were the result of changes in Na+ pump number or turnover rate, we measured binding of [3H]ouabain and ouabain-sensitive 86Rb+ uptake by freshly isolated lung epithelial cells harvested from near-term fetal, newborn, and adult rabbits. Ouabain-sensitive 86Rb+ uptake by fetal cells was 1/4 that of newborn cells and 1/10 that of adult cells. The maximal number of ouabain binding sites (Umax) was the same for fetal and newborn cells but almost threefold greater for adult cells. Na+ pump turnover rate, determined from ouabain-sensitive 86Rb+ uptake and Umax, was four times greater in newborn and adult cells than it was in fetal cells. Thus the increase in 86Rb+ uptake at birth could be explained by an increase in Na(+)-K(+)-adenosinetriphosphatase (ATPase) turnover rate, whereas the postnatal increase in 86Rb+ uptake could be accounted for by an increase in the amount of Na(+)-K(+)-ATPase per cell.
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PMID:Developmental differences in rabbit lung epithelial cell Na(+)-K(+)-ATPase. 217 58

Vitamin E deficiency is a common consequence of chronic cholestatic liver disorders. Inasmuch as vitamin E content of cellular membranes alters membrane properties such as fluidity and molecular order, we postulated that vitamin E status could affect hepatocyte transport processes dependent on membrane integrity. Hepatocytes were isolated from rats maintained on diets containing deficient, sufficient, or excess vitamin E. Cell viability and oxygen consumption were maintained in all groups of hepatocytes. Hepatocyte uptake of taurocholic acid and ouabain and Na+,K(+)-ATPase activity estimated by rubidium-86 influx did not differ with vitamin E status. Vitamin-E-deficient hepatocytes had increased generation of lipid peroxide products. We conclude that deficient or excess vitamin E status had little effect on selected transport processes in normal hepatocytes.
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PMID:Effect of vitamin E on transport processes in isolated rat hepatocytes. 239 66

Specific ouabain binding, active rubidium transport and sodium-lithium countertransport were studied in erythrocytes of 55 normal weight (BMI less than 27), 10 overweight (27 less than or equal to BMI less than 32) and 27 obese (BMI greater than or equal to 32) Finnish subjects after re-examination of the methods. Intra-assay variation coefficients for these three determinations were 6 percent, 6 percent and 12 percent, respectively. When samples from the same subjects were analyzed again after one month interval no significant differences were obtained between the measurements. However, storing of the cells at +4 degrees C increased Na-K-ATPase mediated rubidium transport about 1.5-fold within one day which may partly account for the discrepancies between the previously reported results. Specific ouabain binding of the overweight group appeared to be slightly lower (13.4 percent, P less than 0.05) whereas that of the obese subjects was slightly higher (8.7 percent, P less than 0.05) in comparison with normal weight subjects. Also in active rubidium transport and sodium-lithium countertransport the values of the obese subjects were significantly higher (P less than 0.01, and P less than 0.05, respectively) than those of the normal weight subjects. Furthermore, there existed a significant correlation between active rubidium transport and body mass index (r = 0.34; P less than 0.001) and also between active rubidium transport and specific ouabain binding (r = 0.67; P less than 0.001). In spite of these differences between obese and normal weight subjects there existed considerable overlapping between the groups, and these changes cannot be used as diagnostic tools in screening persons metabolically susceptible to obesity.
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PMID:Red-cell sodium-potassium pump and sodium-lithium countertransport in human obesity. Re-evaluation of the methods and association in a Finnish population. 241 3

An inhibitor of ouabain-insensitive sodium/sodium exchange in erythrocytes has been isolated from leukemic promyelocytes. To explore the specific effects of this inhibitor, named inhibitin, sodium transport experiments were carried out in human erythrocytes. Inhibitin reduced ouabain-insensitive bidirectional sodium transport. It did not change net sodium fluxes, had no significant effect on rubidium influx, and did not inhibit sodium-potassium-ATPase activity. The inhibitory effect of inhibitin was studied on sodium/sodium exchange and on sodium/lithium countertransport in 140 mM sodium and in sodium-free media. In the presence of sodium, inhibitin reduced sodium and lithium efflux to that observed in sodium-free medium. Inhibitin showed no reduction in sodium or lithium efflux when sodium was replaced by choline chloride or Mg2+. When inhibitin was combined with one or more of the other transport inhibitors (i.e., ouabain, furosemide, or bumetanide and amiloride), its inhibitable component remained distinct and it did not overlap with that of the other inhibitors. These studies show that inhibitin is a specific inhibitor of carrier-mediated sodium/sodium exchange and sodium/lithium countertransport processes in human erythrocytes.
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PMID:Inhibitin: a specific inhibitor of sodium/sodium exchange in erythrocytes. 241 64

We have examined the role of the NaK-ATPase pump activity on the ligand-induced down-regulation of gonadotropin receptors in cultured porcine Leydig and Sertoli cells. In both cells, inhibition of the NaK pump by ouabain produced a depletion of intracellular K+ levels (ID50, 10(-7) M) after a lag period of about 8 h. In the absence of ligand, the number of FSH receptors in ouabain-treated Sertoli cells was unaffected or slightly reduced, whereas a 2-fold increase in the number of human CG (hCG)/LH receptors with small changes in the binding affinity was observed in Leydig cells treated by ouabain. The effect of ouabain was dose dependent. Differences were also observed in the down-regulation process of gonadotropin receptors in ouabain-treated cells. The hCG-induced receptor loss in Leydig cells was completely reversed by ouabain whereas the drug had no effect on ligand-induced loss of FSH receptors in Sertoli cells. Similar results were observed when the cells were incubated in K+-free medium. Kinetics studies with labeled hCG have shown that ouabain treatment slows down significantly the rate of [125I]iodo-hCG internalization (t 1/2, 18 h; control cells, t 1/2, 6 h), but had no effect on the degradation of internalized hormone. The internalization of receptor-bound [125I]iodo-hCG was also reduced when Leydig cells were incubated in K+-free medium, but was restored when this medium was supplemented with rubidium. The influence of the NaK pump on the receptor regulation of a ligand common to both types of cells, such as epidermal growth factor, was studied under the same experimental conditions. Neither ouabain nor K+-free medium were able to prevent the epidermal growth factor-induced reduction of receptor levels in Leydig and Sertoli cells. Thus, it appears that modulation of ligand-induced receptor loss by depletion of cellular K+ levels is not dependent on the cell type, but on the ligand-receptor complex. The data also show a striking difference in the dynamics of gonadotropin-receptor interaction of two structurally related hormones.
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PMID:Regulation of gonadotropin receptors on cultured porcine Leydig and Sertoli cells: effect of potassium depletion. 242 17

Using isolated healthy human leucocytes and erythrocytes as model cells, we investigated the inhibitory effect of ethanol, its metabolites and of other toxic alcohols on the active fluxes of rubidium (Rb: equivalent to K) and sodium (Na), and on Na,K-ATPase activity. Ethanol (80 mmol X l-1) inhibited total and ouabain-sensitive 86Rb influx and 22Na efflux in leucocytes, this being dose-related for total, ouabain-sensitive and ouabain-insensitive fluxes at higher concentrations. In erythrocytes inhibition occurred at 20 mmol X l-1 for 86Rb influx, dose-related at higher concentrations as for leucocytes. 22Na efflux was inhibited at 80 mmol X l-1 and above. Acetaldehyde (0.1 and 0.2 mmol X l-1), 1,2-propanediol (0.8 mmol X l-1) and 2,3-butanediol (0.4 mmol X l-1) inhibited all fractions of 86Rb influx in erythrocytes, but not in leucocytes. Methanol, 2-propanol and 1,2-ethanediol (16 and 32 mmol X l-1) inhibited 86Rb influx in erythrocytes, but not in leucocytes. The order of potency was 2-propanol greater than 1,2-ethanediol greater than methanol. Na,K-ATPase activity was inhibited in lysed leucocyte and erythrocyte preparations only at very high concentrations of the alcohols--suggesting that inhibition is due to an alteration in membrane structure and not to a direct effect on the enzyme.
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PMID:The acute in vitro effect of ethanol, its metabolites and other toxic alcohols on ion flux in isolated human leucocytes and erythrocytes. 242 65

Accumulating experimental evidence suggests that natriuresis in response to intravascular volume expansion is promoted by an endogenous regulator of Na+,K+-adenosine triphosphatase (ATPase). Efforts to purify this substance by a number of laboratories have as yet been unsuccessful. The properties of partially purified inhibitors from plasma, urine, and tissue often fail to possess the characteristics thought to be consistent with those of a physiological regulator. These include potency (Ki of approximately 1 nM), reversibility of inhibition, specificity for Na+,K+-ATPase, and responsiveness to relevant physiological stimuli. Two rather different candidate substances, extracted from urine and hypothalamus, have been purified to a high degree. Neither is a peptide, and both are of low molecular weight and resistant to acid hydrolysis. The substance from urine is rather nonpolar and interacts with digoxin-specific antibodies, while that from hypothalamus is polar and does not appear to share epitopes with the cardiac glycosides. On the serosal surface of the toad urinary bladder, the hypothalamic substance causes a reversible inhibition of Na+ transport, inhibits rubidium uptake in red blood cells by acting on the membrane's exterior surface, inhibits binding of ouabain to purified Na+,K+-ATPase, and reversibly inhibits hydrolysis of adenosine 5'-triphosphate by the enzyme with a Ki of 1.4 nM. The hypothalamic inhibitor may be differentiated from ouabain by their respective ionic requirements for optimal inhibition of enzymatic activity, and although both ouabain and the hypothalamic inhibitor fix Na+,K+-ATPase in its E2 conformation, the hypothalamic inhibitor does not promote phosphorylation of the enzyme by inorganic phosphate in the presence of Mg2+. Ionic requirements for inhibition also differentiate the hypothalamic inhibitor from vanadate ion, as does the inhibitor's activity in the presence of norepinephrine. Further enzymological and physiological studies will be facilitated by structural characterizations of the inhibitory substances and by the availability of a method to measure their concentrations in physiological fluids.
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PMID:The search for a hypothalamic Na+,K+-ATPase inhibitor. 243 55

The cultures of Chinese hamster ovary cells (CHO-K1 clone 773) can be brought to the stationary state with most of cellular populations in G1 phase by growing continuously for 4 days up to the cultural density (10-12) X 10(4) cells/cm2. Upon introduction of fresh Eagle medium with 10% calf serum the cells progress from G1 to S phase for 7-9 hours. It is shown that within the first minutes of serum addition ouabain-sensitive rubidium influx increases, however, lithium influx, which serves a test for passive sodium pathways in the membrane, increases or does not change. No correlation was found between the rubidium influx and intracellular sodium changes, induced by serum. From comparative studies of ouabain-sensitive rubidium influx, lithium influx and intracellular sodium content it is concluded that the increase in intracellular sodium is not responsible for serum-induced Na,K-ATPase activation.
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PMID:[Cation transport and content in serum-stimulated CHO-773 cells. I. Rapid changes in rubidium and lithium influxes and intracellular sodium content]. 243 68

Serum stimulation of stationary cultures of Chinese hamster ovary cells CHO-K1 (clone 773) is accompanied by sustained increase in ouabain-sensitive rubidium (potassium) influx which results in the elevation of intracellular potassium content from 0.5-0.6 to 0.7-0.8 mmole per gram of protein. Cytofluorometric studies of serum-stimulated CHO-773 cultures have shown that the intracellular potassium increase is necessary for successful G1----S progression. The elevation of intracellular potassium was found to occur simultaneously with the cellular protein growth. Cycloheximide (10 micrograms/ml) does not influence the early Na,K-ATPase activation induced by serum; however, it abolishes the sustained increase of both rubidium influx and intracellular potassium content. In serum stimulated cells ouabain increases the potassium efflux; this ouabain effect is not observed after S phase, when rubidium (potassium) influx decreases and intracellular potassium content stops growing.
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PMID:[Cation transport and content in serum-stimulated CHO-773 cells. II. Late changes in rubidium influx and intracellular potassium content]. 243 75


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