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)

The renal effects of sodium vanadate (Na3VO4), an inhibitor of sodium-potassium-ATPase recently shown to be a potent diuretic, were studied by using clearance and micropuncture techniques in nondiuretic anesthetized rats. Administration of 1.0 mumole of sodium vanadate (high dose) increased urine flow rate (V) from 9.8 +/- 1.4 to 17.5 +/- 4.0 microliter/min (mean +/- SEM, P < 0.025), UNaF from 1.73 +/- 0.36 to 3.05 +/- 0.65 microEq/min (P < 0.025), and FENa from 0.67 +/- 0.15 to 1.24 +/- 0.28% (P < 0.025)., No significant changes in GFR or RPF were observed. Late proximal tubular-fluid-to-plasma (F/P) inulin decreased from 2.28 +/- 0.19 to a minimum value of 1.38 +/- 0.06 (P < 0.025). Absolute water reabsorption decreased from 15.8 +/- 3.5 to 6.5 +/- 1.7 nl/min (P < 0.025) and fractional water reabsorption from 52.0 +/- 4.4 to 26.5 +/- 4.1% (P < 0.025). The injection of 0.5 mumole of sodium vanadate (low dose) resulted in no significant changes in V. Late proximal F/P inulin decreased, however, from 2.37 +/- 0.14 to a minimum value of 1.59 +/- 0.12 (P < 0.025). SNGFR remained unchanged, as did GFR and RPF. UNaV increased from 1.41 +/- 0.35 to 2.25 +/- 0.35 microEq/min (P < 0.025), and FENa rose from 0.64 +/- 0.16 to 0.91 +/- 0.15% (P < 0.025). The decrease in F/P inulin was observed in all but one animal, even in the absence of a diuretic response. The amount of fluid remaining in the lumen of the late proximal tubule was virtually the same in both low- and high-dose animals (18.9 +/- 3.0 and 19.5 +/- 3.4 nl/min, respectively). We conclude that sodium vanadate causes a decrease in superficial proximal tubule fluid and salt reabsorption. Inasmuch as the low dose does not result necessarily in a diuretic response, an increase in fluid reabsorption distal to the late proximal tubule must take place.
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PMID:Effects of sodium orthovanadate on whole kidney and single nephron function. 690 86

Previous studies have demonstrated abnormalities of intracellular electrolyte content and sodium transport in leukocytes of patients with fulminant hepatic failure. The current study was undertaken to establish whether similar abnormalities were present in patients with encephalopathy from advanced cirrhosis. Results from 19 patients with advanced cirrhosis showed values for the leukocyte total sodium efflux-rate constant were significantly reduced in patients, 3.02 +/- 1 SEM 0.12 h-1, compared to control values, 3.80 +/- 0.06 h-1. This reduction was due primarily to a lowering of the ouabain-sensitive component of sodium efflux, a measure of Na,K-ATPase activity. In comparison, leukocytes from patients with fulminant hepatic failure show a greater inhibition of the ouabain-sensitive component of sodium efflux with a raised ouabain-insensitive efflux. Although cirrhosis has generally been associated with potassium depletion, the intracellular potassium content of the cirrhotic patients' leukocytes was normal. Since the leukocyte is considered to be a good cell model and because abnormalities of sodium transport have been shown in the leukocytes of these patients, it is likely that similar abnormalities of sodium transport are present in other organs, including the brain.
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PMID:Abnormalities in the leukocyte sodium pump in advanced cirrhosis. 726 13

Intracellular Ca2+ pools contribute to changes in cytosolic [Ca2+] ([Ca2+]i), which play an important role in endothelial cell signaling. Recently, endothelial ryanodine-sensitive Ca2+ stores were shown to regulate agonist-sensitive intracellular Ca2+ pools. Since caffeine binds the ryanodine Ca2+ release channel on the endoplasmic reticulum in a variety of cell types, we examined the effect of caffeine on [Ca2+]i in human aortic endothelial cell monolayers loaded with the fluorescent probe indo 1. Under baseline conditions, 10 mmol/L caffeine induced a small increase in [Ca2+]i from 86 +/- 10 to 115 +/- 17 nmol/L (mean +/- SEM); this effect was similar to that of 5 mumol/L ryanodine and was unaffected by buffer Ca2+ removal. After depletion of an intracellular Ca2+ store by the irreversible endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin (1 mumol/L), ryanodine did not affect [Ca2+]i. In contrast, caffeine induced a large rapid increase in [Ca2+]i (176 +/- 19 to 338 +/- 35 nmol/L, P < .001) after thapsigargin exposure; this effect of caffeine was only observed when extracellular Ca2+ was present. A similar increase in [Ca2+]i was induced by caffeine after depletion of ryanodine- and histamine-sensitive Ca2+ stores or after pretreatment with the endoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid (10 mumol/L). Thus, under baseline conditions the effect of caffeine on [Ca2+]i is similar to that of ryanodine and appears to be due to the release of an intracellular store. However, after depletion of an endoplasmic reticulum Ca2+ store, caffeine, but not ryanodine, stimulates Ca2+ influx, resulting in a large increase in [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endoplasmic reticulum Ca2+ depletion unmasks a caffeine-induced Ca2+ influx in human aortic endothelial cells. 755 46

Intracellular passive Ca2+, buffering was measured in voltage-clamped rat ventricular myocytes. Cells were loaded with indo-1 (K+ salt) to an estimated cytosolic concentration of 44 +/- 5 microM (Mean +/- SEM, n = 5), and accessible cell volume was estimated to be 24.5 +/- 3.6 pl. Ca2+ transport by the sarcoplasmic reticulum (SR) Ca-ATPase and sarcolemmal Na-Ca exchange was inhibited by treatment with thapsigargin and Na-free solutions, respectively. Extracellular [Ca2+] was maintained at 10 mM and, in some experiments, the mitochondrial uncoupler "1799" was used to assess the degree of mitochondrial Ca2+ uptake. To perform single cell titrations, intracellular Ca2+ ([Ca2+]i) was increased progressively by a train of depolarizing voltage clamp pulses from -40 to +10 mV. The total Ca2+ gain with each pulse was calculated by integration of the Ca current and then analyzed as a function of the rapid change in [Ca2+]i during the pulse. In the range of [Ca2+]i from 0.1 to 2 microM, overall cell buffering was well described as a single lumped Michaelis-Menten type species with an apparent dissociation constant, KD, of of 0.63 +/- 0.07 microM (n = 5) and a binding capacity, Bmax, of 162 +/- 15 mumol/l cell H2O. Correction for buffering attributable to cytosolic indo-1 gives intrinsic cytosolic Ca2+ buffering parameters of KD = 0.96 +/- 0.18 microM and Bmax = 123 +/- 18 mumol/l cell H2O. The fast Ca2+ buffering measured in this manner agrees reasonably with the characteristics of known rapid Ca buffers (e.g., troponin C, calmodulin, and SR Ca-ATPase), but is only about half of the total Ca2+ buffering measured at equilibrium. Inclusion of slow Ca buffers such as the Ca/Mg sites on troponin C and myosin can account for the differences between fast Ca2+ buffering in phase with the Ca current measured in the present experiments and equilibrium Ca2+ buffering. The present data indicate that a rapid rise of [Ca2+]i from 0.1 to 1 microM during a contraction requires approximately 50 microM Ca2+ to be added to the cytosol.
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PMID:Intrinsic cytosolic calcium buffering properties of single rat cardiac myocytes. 781 10

Rabbit corneal endothelial cells mounted in vitro were impaled simultaneously with Na(+)-selective and conventional KCl-filled microelectrodes. The membrane potential (Vm) was -30.4 +/- 0.8 mV (mean +/- SEM, n = 55) and the intracellular [Na+]i (calculated from the Na(+)-selective electrode potential, VNa) was 13.7 +/- 1.9 mM (mean +/- SEM, n = 16). When ouabain was added to the perfusate the cell depolarised, causing both Vm and VNa to increase with a very similar time course. Final Vm was -6.3 +/- 0.6 mV (mean +/- SEM, n = 15), and the final [Na+]i was 114 +/- 6.9 mM (mean +/- SEM, n = 5). The parallel increase in Vm and rise in [Na+]i suggest that a component of the ouabain-induced depolarisation of the cell (increase in Vm) is due to Na+ entry into the cell down its concentration gradient. The lateral and basal location of the Na+/K(+)-ATPase in bovine endothelial cells was confirmed (for the first time at the electron-microscopic level) using a monoclonal antibody specific for the alpha 1 subunit of Na+/K(+)-ATPase. The absence of a net Na+ flux across these cells combined with the basolateral location of the ATPase suggest that Na+ exit from the cell, and its re-entry take place across the same membrane (i. e. the basolateral).
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PMID:Sodium movement into and out of corneal endothelium. 783 80

Experimental diabetes in rodents is associated with diminished activity of sodium-potassium-adenosine triphosphatase (Na+ -K+ -ATPase) in the sciatic nerve, an abnormality that has been invoked as being factorial in the genesis of diabetic peripheral neuropathy. Whether a parallel metabolic abnormality occurs in the autonomic vagus nerve is unknown. To answer this question, adult male rats made diabetic with streptozotocin (45 mg/kg) and age-matched nondiabetic controls were killed at 1 and 3 months after induction of diabetes. The cervical vagi and sciatic nerves were excised, weighed, and homogenized, and Na+ -K+ -ATPase activities were determined. After 1 month, the diabetic animals showed a significantly reduced sciatic nerve Na+ -K+ -ATPase activity as compared with respective controls, whether expressed in micromoles per gram wet weight per hour (20.5 +/- 4.9 [mean +/- SEM] vs 61.6 +/- 13.0) or micromoles per milligram of protein per hour (0.77 +/- 0.21 vs 2.48 +/- 0.57, p < 0.05, diabetic vs control, respectively). Diabetic vagus nerve Na+ -K+ -ATPase activity was also diminished (40.6 +/- 6.9 mumol/gm wet weight per hour vs 63.2 +/- 9.7 mumol/gm wet weight per hour and 3.83 +/- 0.81 mumol/mg protein per hour vs 5.86 +/- 0.73 mumol/mg protein per hour), but the results did not reach statistical significance. After 3 months, diabetic sciatic nerve Na+ -K+ -ATPase activity was still significantly less than the control group value (16.89 +/- 3.91 mumol/mg wet weight per hour vs 38.9 +/- 4.24 mumol/gm wet weight per hour and 0.48 +/- 0.11 mumol/mg protein per hour vs 1.04 +/- 0.14 mumol/mg protein per hour; p < 0.05, diabetic vs control, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired rodent vagal nerve sodium-potassium-ATPase activity in streptozotocin diabetes. 784 68

The injury and recovery processes of complex reactions of liver mitochondrial ATP synthesis during warm ischemia and after reflow were studied separately in terms of the changes in oxidation (electron transfer system) and phosphorylation (H(+)-ATPase). Oxidative activity decreased significantly from the control value of 40 +/- 0.9 (mean +/- SEM, n = 5) to 31.5 +/- 1.13 (nanoatoms oxygen consumed/min/mg protein) after 40 min of warm ischemia, while phosphorylative activity decreased significantly from the control value of 1.06 +/- 0.12 to 0.42 +/- 0.03 (mumole ATP hydrolyzed/min/mg protein) after 20 min of warm ischemia. During 120 min of reflow after 20 min of warm ischemia, the decreased phosphorylation activity recovered to 0.52 +/- 0.01 concomitant with a recovery of intramitochondrial total adenine nucleotide and an increase in the ATP/ADP ratio, while oxidative activity decreased further to 23.9 +/- 0.81. These results indicate that H(+)-ATPase is more vulnerable to warm ischemia than the electron transfer system, but that it is restored concomitant with the recovery of intramitochondrial adenine nucleotide content.
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PMID:Primary and reversible injury of H(+)-ATPase in warm ischemia and reperfusion of rat liver in relation to intramitochondrial adenine nucleotide. 786 69

To investigate the peripheral metabolic status during normal pregnancy, we measured the number of erythrocyte Na,K-ATPase units as well as the cation transport activity of the pump from 32 normal pregnant women and 12 normal controls. The number of pump units determined by maximal ouabain binding to erythrocyte in normal pregnancy was significantly higher than that in normal controls (mean +/- SEM: 0.52 +/- 0.03 vs. 0.39 +/- 0.04 pmol/10(9)RBC, P < 0.05). The total cation transport activity of the pump measured by 86Rb uptake also significantly increased during pregnancy (98.9 +/- 6.4 vs. 73.1 +/- 5.4 nmol/10(9) RBC, P < 0.01). However, the mean cation transport activity per pump unit, which was presumed to be an indicator of the peripheral metabolic status, was unchanged in any of three trimesters when compared with that in normal controls. Serum FT4 levels measured by two different methods were significantly lower in the third trimester than in the first trimester (P < 0.01). In conclusion, erythrocyte Na, K-ATPase activity per pump unit is normal in pregnant women, suggesting that the peripheral metabolic status in pregnancy seems to be normal. Increases in both the number and function of the pump may be influenced by factors other than thyroid function.
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PMID:Measurement of erythrocyte Na,K-ATPase activity in normal pregnant women. 795 92

Brush border (BBM) and basolateral membranes (BLM) of rat renal cortical cells separated by free flow electrophoresis revealed two distinct peaks of BBM-specific leucine aminopeptidase and Na+/K(+)-ATPase for BLM. PTH/PTH-related protein (PTHrP) receptors were identified in BBM and BLM. Specific binding of 125 pM [125I]chicken [Tyr36]-PTHrP-(1-36)amide [chPTHrP-(1-36)] to individual fractions of membranes separated by free flow electrophoresis overlapped with the leucine aminopeptidase and Na+/K(+)-ATPase profiles. Binding to pooled BBM was 53 +/- 5% (mean +/- SEM) of that to BLM (P < 0.01). In BBM and BLM, half-maximal inhibition of binding was obtained with 0.4-0.9 nM chPTHrP-(1-36) and 0.2-0.6 nM rat PTH-(1-34). Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; 100 microM) lowered chPTHrP-(1-36) binding to 50% of control levels, and half-maximal inhibition of binding was obtained with 480 and 8 nM GTP gamma S in BBM and BLM, respectively. Cross-linking of the PTH/PTHrP receptors with [125I]chPTHrP-(1-36) modified with N-hydroxysuccinimidyl-4-azidobenzoate revealed indistinguishable doublets of 83 and 73 kilodaltons in both BBM and BLM. Adenylyl cyclase was stimulated 6- and 10-fold by chPTHrP-(1-36) and GTP gamma S, respectively, in BLM and 1.3- and 1.9-fold in BBM. In conclusion, PTH receptors were recognized in both the basolateral and brush border membranes. Different receptor coupling to G-proteins and minimal cAMP stimulation in BBM provide evidence for PTH/PTHrP receptor isotypes and/or different postreceptor activation in BBM and BLM.
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PMID:Apical and basolateral parathyroid hormone receptors in rat renal cortical membranes. 811 56

The temporal pattern of changes in the specific activities of retinal Na+, K(+)-ATPase (Na, K-ATPase) and Mg(2+)-ATPase (Mg-ATPase) were determined at several time intervals following the onset of diabetes in streptozotocin-induced diabetic (STZ: at 1, 2, 4 and 6 months) Long-Evans hooded rats, spontaneously diabetic Zucker diabetic fatty (ZDF: at 1, 2 and 4 months) rats and their age-matched controls. These animals were utilized as models for insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), respectively. Na, K-ATPase specific activity, using 10(3) M ouabain, was decreased (-6% to -14%) at all time points after the appearance of hyperglycemia in the ZDF rat, but was reduced only after 4 and 6 months in the STZ rat (-8% and -14%, respectively). In contrast, Mg-ATPase activity was significantly increased (13%) after 4 months in the ZDF rat and after 6 months in the STZ rat (8%). The concentration-dependent inhibitory effects of ouabain (10(-9) to 10(-3) M) on the activity of Na, K-ATPase in diabetic rats and age-matched controls was used to assess the time-dependent effects of diabetes on the alpha 3-high ouabain affinity or the alpha 1-low ouabain affinity retinal Na, K-ATPase isozymes. The retinal Na, K-ATPase activity for the alpha 3 isozyme was significantly lower at all times examined for the ZDF (-5% to -26%) and STZ-induced diabetic rats (-8% to -14%). This was reflected in the markedly decreased half-maximal inhibitory concentrations (IC50) of ouabain for the alpha 3 isozyme. For example, after four months of diabetes, the mean +/- SEM IC50 values were 12 +/- 3 nM in the STZ rats and 48 +/- 6 nM in the age-matched controls and 19 +/- 3 nM in the ZDF rats and 30 +/- 4 nM in the age-matched controls. In contrast, the activity of the alpha 1 isozyme was slightly, but significantly, decreased at 2 and 4 months in the ZDF rats (-4% to -7%) and after 4 and 6 months in the STZ-induced diabetic rats (-3% to -9%) while the IC50 values were unchanged. Moreover, the Hill coefficient for the alpha 3 isozyme was decreased in both diabetic groups while it was unchanged for the alpha 1 isozyme.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Alterations in retinal Na+, K(+)-ATPase in diabetes: streptozotocin-induced and Zucker diabetic fatty rats. 813 34


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