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)

A potent (Na,K)-ATPase inhibitor purified from "Sigma Grade* ATP has been identified as vanadium using electron probe microanalysis and confirmed by microwave-induced emission spectroscopy and electron paramagnetic resonance spectroscopy. Sodium orthovanadate (Na3 VO4) is identical with the purified inhibitor with respect to ultraviolet absorbance, migration on thin layer chromatography, and inhibition of (Na,K)-ATPase. The (Na,K)-ATPase is in-inhibited 50% by 40 nM Na3 VO4 under optimal conditions (28 mM Mg2+) and the inhibition is 100% reversible by millimolar concentrations of norepinephrine. The physiological significance of this inhibition is discussed in relation to vanadium concentrations in vivo.
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PMID:Vanadate is a potent (Na,K)-ATPase inhibitor found in ATP derived from muscle. 14 27

The motility of demembranated sea urchin sperm flagella and that of embryo cilia reactivated with 0.1 mM ATP are completely inhibited by 4 micron and 0.5 micron vanadium(V) [V(V), in vanadate], respectively. The Mg2+-activated ATPase activity (ATP phosphohydrolase, EC 3.6.1.3)of the latent form of dynein 1 is inhibited 50% by 0.5-1 micron V(V), while the Ca2+-activated ATPase activity is much less sensitive. The inhibition of flagellar beat frequency and of dynein 1 ATPase activity by V(V) appears not to be competitive with ATP. In agreement with other reports, the inhibition of (Na,K)-ATPase by V(V) shows a slow onset in the presence of ATP and is relatively rapid in its absence. With dynein, however, the inhibition occurs at a rapid rate whether or not ATP is present. Catechol at a concentration of 1 mM reverses the V(V) inhibition of reactivated sperm motility, dynein ATPase, and (Na, K)-ATPase. Myosin and actomyosin ATPases show no inhibition by concentrations of V(V) up to 500 micron. The inhibition by V(V) provides a possible technique for distinguishing between the actions of dynein and myosin in different forms of cell motility.
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PMID:Potent inhibition of dynein adenosinetriphosphatase and of the motility of cilia and sperm flagella by vanadate. 14 86

Inhibition of adenosinetriphosphatase (ATPase) by vanadium pentoxide (dissolved in water or in sodium hydroxide solution) was studied in microsomal fractions and tissue homogenates of kidney, brain, and heart of several species, including humans (kidney only). In some preparations vanadium was found to be the most potent inhibitor of Na+ + K+ATPase activity so far reported. Concentrations of vanadium causing 50 percent inhibition of Na+ + K+ATPase activity ranged from 6 x 10(-8) to 5 x 10(-7) M in microsomal fractions and from 2 x 10(-7) to 1 x 10(-6) M in tissue homogenates. Renal and cardiac enzymes were more sensitive to vanadium than the brain enzyme, a phenomenon independent of enzyme specific activity. The enzyme in tissue homogenates was more resistant to vanadium than the microsomal enzyme derived from the same tissues, suggesting a presence in tissues of protective agents. Mg2+ ATPase, which contaminated the enzyme preparations to a variable degree, was 1,000-10,000 times more resistant to vanadium than was Na+ + K+ATPase. More detailed studies on the mechanism of inhibition were performed with dog and human kidney enzymes. The reversible nature of the inhibition was suggested by the fact that fractional inactivation of Na+ + K+ATPase by vanadium was independent of enzyme protein concentrations. The inhibitory effect was reduced by Na+ and increased by K+ or Mg2+. ATP alone, but not MgATP, antagonized the inhibition. This could mean that vanadium inhibits the Na+ + K+ATPase at the site activated by Na+, and that ATP protects the enzyme either by binding vanadium or by competing for a mutual receptor on the enzyme. The inhibition was reduced by bovine serum albumin, probably binding vanadium. The inhibition was also diminished by reducing agents, ascorbic acid and citric acid.
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PMID:Inhibition by vanadium of sodium and potassium dependent adenosinetriphosphatase derived from animal and human tissues. 21 60

The fate of vanadate (+5 oxidation state of vanadium) taken up by the red cell was studied using EPR spectroscopy. The appearance of an EPR signal indicated that most of the cytoplasmic vanadate is reduced to the +4 oxidation state with axial symmetry characteristic of vanadyl ions. The signal at 23 degrees C was characteristic of an immobilized system indicating that the vanadyl ions in the cytoplasm are associated with a large molecule. [48V]Vanadium eluted with hemoglobin when the lysate from Na3[48V[O4-treated red cells was passed through a Sephadex G-100 column and rabbit anti-human hemoglobin serum caused a hemoglobin-specific precipitation of 48V when added to the red cell lysate. Both results indicate that hemoglobin is the protein which binds cytoplasmic vanadyl ions. However, neither sodium vanadate nor vanadyl sulfate bound to purified hemoglobin in vitro. Finally, transient kinetics of vanadyl sulfate interaction with the sodium-and potassium-stimulated adenosine triphosphatase showed that the +4 oxidation state of vanadium is less effective than the +5 oxidation state in inhibiting this enzyme. These results indicate that oxidation-reduction reactions in the cytoplasm are capable of relieving vanadate inhibition of cation transport.
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PMID:The fate of cytoplasmic vanadium. Implications on (NA,K)-ATPase inhibition. 21 70

Vanadium in the 4+ (vanadyl-ion) and 5+ (vanadate-ion) oxidation state stimulates furosemide-sensitive electrogenic Cl- secretion in isolated epithelia of rabbit descending colon. This effect is associated with an increased release of prostaglandin E2 from the tissue. Inhibitors of phospholipase A2 or cyclooxygenase abolish both vanadium-induced release of prostaglandin E2 and Cl- secretion. Neuronal mechanisms are not likely to be involved, as tetrodotoxin does not affect the vanadate induced Cl- secretion. Although vanadate is known to inhibit Na+,K(+)-ATPase activity, no inhibition of active Na+ transport was observed in intact colonic epithelia suggesting a rapid intracellular reduction of vanadate ions to vanadyl ions which have no inhibitory effect on the Na+,K(+)-ATPase. The present findings therefore indicate that vanadate stimulated colonic Cl- secretion involves intracellular conversion of vanadate to vanadyl and release of prostaglandin E2.
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PMID:Vanadium-induced Cl(-)-secretion in rabbit descending colon is mediated by prostaglandins. 161 17

Vanadium (V) has been reported to inhibit a number of enzyme activities such as those of Na(+)-K(+)-ATPase. The main excretory pathway of this element is via the kidney. These facts led us to study the V distribution in uremic patients. As a result, hemodialysis patients at our dialysis center exhibited extremely high levels of serum V (23.9 +/- 11.3 ng/ml, n = 43) as compared with healthy adults. Nondialysis patients did not show increased serum V concentrations. The V contents were significantly elevated in the skin and in the aortae of hemodialysis patients. It was found that the tap water from Kanagawa prefecture, Japan, had the highest V concentrations among the 21 cities in Japan and the US. In conclusion, oral ingestion of V-contaminated water has likely caused an accumulation of the metal in patients with end-stage renal failure.
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PMID:Abnormal accumulation of vanadium in patients on chronic hemodialysis therapy. 207 94

Red blood cell (RBC) calcium, calcium 45 influx, and calcium extrusion as indicated by Ca-stimulated, Mg-dependent adenosine triphosphatase (CaATPase) was determined in patients with chronic renal failure (CRF), patients with CRF receiving continuous ambulatory peritoneal dialysis (CAPD) treatment, and controls. Cell calcium, which in the controls was 5.5 mumol/L of cells, was elevated in patients with CRF--30.6 +/- 6.8 mumol/L of cells (p less than 0.002)--and in patients receiving CAPD-23.6 +/- 6.7 mumol/L of cells (p less than 0.02). Basal CaATPase activity in controls was 850.7 +/- 66.7 nmol inorganic phosphate per milligram of protein per hour. It was suppressed in patients with CRF and patients receiving CAPD: 504.9 +/- 34.4 nmol inorganic phosphate per milligram of protein per hour and 618.2 +/- 47.3 nmol inorganic phosphate per milligram of protein per hour, respectively (p less than 0.01). Calmodulin-stimulated CaATPase revealed a pattern similar to that of CaATPase basal activity. RBC calcium showed an inverse correlation with CaATPase activity (r = -0.935, p less than 0.005) in patients with CRF. Calcium influx was increased in patients with CRF and in patients receiving CAPD: 12.00 +/- 1.34 mumol/L of cells per hour and 13.60 +/- 1.70, respectively, compared with 4.61 +/- 0.39 mumol/L of cells per hour in controls (p less than 0.001). Patients with CRF have elevated RBC calcium levels mainly related to decreased extrusion and to increased influx. CAPD fails to improve substantially these abnormalities. Plasma vanadium levels were markedly elevated in patients undergoing hemodialysis and marginally in patients receiving CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Red blood cell calcium level in chronic renal failure: effect of continuous ambulatory peritoneal dialysis. 214 69

Since it has been claimed that vanadate is an endogenous regulator of Na/K-ATPase activity and that it potentiates the toxicity of cardiac glycosides, we were alarmed to discover that certain Finnish physicians were prescribing vanadate in combination with other trace minerals to elderly patients for many different chronic diseases (e.g., cancer, rheumatism). To study the interaction of vanadate and cardiac glycosides, we fed vanadate in the drinking water (25 micrograms/mL) to guinea pigs for 20 d, and studied either their sensitivity to the acute toxicity of the cardiac glycoside ouabain or whether the vanadate would influence the subacute toxicity of ouabain. Vanadate had no influence on the toxicity of ouabain either acute or subchronically administered, nor was there any sign of inhibition of Na/K-ATPase activity as measured by 86Rb-uptake into intact erythrocytes (RBCs), RBC content of sodium or potassium or Na/K-ATPase activity in RBC membranes prepared from the vanadate-treated guinea pigs. Vanadate had been absorbed in substantial quantities from the gastrointestinal tract, since serum, heart, liver, and especially kidney contained measurable amounts of vanadium in contrast to controls, but it is concluded that this vanadate is not in a biologically active form.
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PMID:Subchronic treatment with vanadate does not potentiate the toxicity of cardiac glycosides. 248 47

1. Vanadate and vanadyl ions (10(-5)-10(-2) M) induced dose-dependent rhythmic contractions of the vas deferens of reserpine-treated guinea-pigs. The Na, K-ATPase blocker ouabain (10(-5)-10(-3) M) induced similar, though smaller, effects. Experiments were performed to verify if these effects are due to an interaction with the same receptor population. 2. Ouabain caused a striking potentiation of vanadium effects, which was also observed in denervated organs, indicating that a release of neuronal substances is not involved in potentiation. Similar potentiations were observed by combining vanadium with K-free solutions instead of ouabain, corroborating the involvement of the latter drug with Na, K, ATPase. 3. From the analysis of time-response and concentration-response curves, there are at least three indications that vanadium and ouabain interact with different sites: (a) the combined effect of both agonists was several times higher than the corresponding isolated effects; (b) the combined effect, expected to be independent of the order of addition of the agonist, was higher if vanadium was added before, than after ouabain; (c) the combined effect on the time elapsed between the addition of the two agonists, being higher if an interval of at least 10 min was allowed between vanadium and ouabain additions. 4. In conclusion, our results do not support the hypothesis that vanadium compounds and ouabain have a similar mechanism of action for the contraction induced in guinea-pig vas deferens.
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PMID:Contractile responses of the guinea-pig vas deferens to the combination of vanadium ions with ouabain. 275 43

Three studies are reported. In study 1, vanadium concentration was estimated by neutron activation analysis in hair, whole blood, serum and urine from 13 patients suffering from depressive psychosis and then when on recovery. Vanadium concentration of hair, whole blood and serum decreased significantly with recovery, but there was no significant change in 24-h urinary excretion or in renal clearance of vanadium. In study 2, vanadium concentration was estimated by neutron activation analysis in serum and urine of 31 patients with depressive psychosis and of 27 normal controls. Mean renal clearance of vanadium was significantly lower and mean serum vanadium concentration significantly higher in depressed patients than in controls. Mean 24-h excretion of vanadium did not differ between the two groups. Vanadium excretion did not correlate with urine volume, with serum concentration or with age. In study 3, erythrocyte Na-K ATPase activity and serum vanadium concentrations were estimated in 58 patients. There was a strong negative correlation between the two, supporting the suggestion that changes in tissue vanadium concentration may explain the changes in sodium transport which occur in depressive psychosis.
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PMID:Further studies of vanadium in depressive psychosis. 282 May 35


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