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)

1. The mechanisms involved in the responses induced by sodium vanadate (Va3 VO4) on cat cerebral and femoral arteries were studied. The possibility that these responses were due to Na+, K+-ATPase inhibition was investigated by measuring the effect of vanadate on [3H]-ouabain binding to arterial membrane fractions, K+-induced vasodilatation and ouabain-sensitive 86Rb+ uptake. 2. The vanadium compounds (Na3VO4, VOSO4, VCl3 and O5V3) induced similar, concentration-dependent contractions in each kind of artery, the cerebral vessels being the most sensitive to these compounds. 3. Exposure of the arteries to a low-Na+ (25 mM) solution suppressed the contraction caused by vanadate in femoral but not in cerebral arteries. 4. Vanadate-induced contractions were reduced in Ca2+-free medium but remained unaffected by 3 x 10(-6) M phentolamine, reserpine pretreatment or 3 x 10(-6) M verapamil in both kinds of artery. 5. The addition of 7.5 mM K+ to the arteries immersed in a K+-free solution induced vasodilatation, which was not modified by 10(-3) M vanadate. 6. The consecutive administration of ouabain (10(-4) M) and vanadate (10(-3) M) (or vice versa), or the simultaneous administration of both agents (10(-8) to 10(-3) M) appeared to produce an additive contraction in both types of artery. 7. Vanadate (10(-7) to 10(-3) M) did not displace the [3H]-ouabain binding to arterial membrane fractions of these arteries, whereas 10(-4) M ouabain did. 8. In both kinds of artery, total 86Rb+ uptake was reduced by ouabain (10(-8) to 10(-3) M), in a concentration-dependent manner, whereas it was not modified by vanadate (10(-8)-10(-3) M). 9. These results suggest that vanadate induces contraction in both types of artery by a mechanism unrelated to Na+, K+-ATPase inhibition. Such a mechanism is likely to be related to inhibition of the Ca2-ATPase of the cell membrane and/or the sarcoplasmic reticulum.
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PMID:Actions of vanadate on vascular tension and sodium pump activity in cat isolated cerebral and femoral arteries. 334 33

The effect of vanadate (VO-3), an "in vitro" inhibitor of Na,K-ATPase activity, on sodium and water intake and excretion of Na-depleted and water deprived rats, was investigated. Injection of sodium orthovanadate Na3V04, H20 14) 1 microliter, 1.0 mM solution, 51 ng/microliter free base vanadium (V) into the 3rd brain ventricle (3BV) inhibited by 34% the sodium intake induced by peritoneal dialysis (PD). Urinary water and sodium excretion increased and potassium excretion decreased. The same concentration of vanadate administered by continuous infusion into the 3BV (1 microliter/hr, 24 hr, 51 ng/microliter, 1.2 micrograms/24 hr) during 24 hours after PD, decreased sodium intake by 69%. The same rate of infusion through the jugular vein failed to inhibit sodium intake or to increase urinary water and sodium excretion. Injections into lateral hypothalamus were also ineffective. Vanadyl (VO+2), the reduced form of vanadate, did not affect sodium intake. Similar or larger doses of vanadate injected into the 3BV of water deprived rats, did not modify water intake significantly. The present results suggest that the Na-K, active transport system is involved in salt and water balance regulation at the central nervous system level.
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PMID:Effect of intracerebroventricular vanadate administration on salt and water intake and excretion in the rat. 348 53

The activity of Na,K-ATPase was measured in brain microsomes as the function of increasing concentrations of vanadyl (VOSO4, V4+) and the vanadate (NaVO3, V5+) ions. Both forms of vanadium inhibited the Na,K-ATPase activity with high affinity -Ki (vanadate) = 3 X 10(-7)M and Ki (vanadyl = 1 X 10(-6)M. The stability of V4+ in ATPase reaction media (Tris buffers) was measured by electron spin resonance spectroscopy. Without any reducing agent, V4+ was quickly oxidised by atmospheric oxygen. When a reducing agent such as dithiothreitol was added, the V4+ was stable for at least 30 min and the inhibition pattern of Na,K-ATPase by V4+ was not changed. The blocking effect of V4+ in the presence of dithiothreitol was counteracted by pre-incubation with equimolar concentrations of transferrin or 100 times excess of noradrenaline. The regulation of brain Na,K-ATPase by vanadate may be represented by competition between low-capacity inhibitory binding sites localized on the enzyme molecule and high-capacity sites of intracellular proteins. Preferential binding of vanadyl to the latter type of sites will decrease the intracellular concentration of the free metal and thus eliminate the enzyme inhibition.
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PMID:Vanadyl (VO2+) and vanadate (VO-3) ions inhibit the brain microsomal Na,K-ATPase with similar affinities. Protection by transferrin and noradrenaline. 608 31

Inhibitory action of vanadate (orthovanadate and metavanadate) on ciliary dynein adenosinetriphosphatase (ATPase) from Tetrahymena was investigated. The apparent concentrations of vanadate giving half-maximal inhibition of Mg-ATPase activity of various dynein fractions were as follows: the axoneme-bound form of dynein at 100 nM, solubilized crude dynein at 50 nM, 14S dynein at 5 microM, and 30S dynein at 20 nM. The Ca-ATPase of 30S dynein was more than 30-fold less sensitive than its Mg-ATPase, and still less sensitive was the Ca-ATPase of 14S dynein. The Mg-ATPase of 30S dynein was most sensitive to vanadate at neutral pH, and the addition of KCl or NaCl into the assay mixture reduced its sensitivity. Varying the assay temperature between 0 and 37 degrees C affected the sensitivity to a slight extent. Metavanadate was as much a potent inhibitor of dynein ATPase as orthovanadate, but vanadium pentoxide was less potent. When the dynein ATPase activity was reciprocally plotted against the concentration of vanadate (the Dixon plot), the inhibition was proved to be biphasic. At lower concentrations of vanadate, the inhibition was more significant. Therefore the Dixon plot had a downward bent. Reexamination of the Lineweaver-Burk plot of 30S dynein Mg-ATP showed a downward bent, which indicates that 30S dynein may have at least two Km values, ca. 1 microM and 3 microM; or otherwise, 30S dynein might possibly have a negatively cooperative nature (Hill coefficient 0.67). The vanadate-induced inhibition of 30S dynein Mg-ATPase was noncompetitive in the entire range of ATP concentration examined. Since the vanadate-induced inhibition of 30S dynein Mg-ATPase could be classified into "tight-binding inhibition", we could estimate the dissociation constant of vanadate and the molecular weight per enzymatic active site according to the kinetics of tight-binding inhibition with several assumptions. Thus, the dissociation constant was 10-15 nM, depending on the ATPase assay condition, while the molecular weight per enzymatic active site was 420 000-480 000, independent of the assay condition with the assumption that the present 30S dynein preparation is totally pure. This value would be reduced about 20% when the purity was taken into consideration.
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PMID:Steady-state kinetic study of vanadate-induced inhibition of ciliary dynein adenosinetriphosphatase activity from Tetrahymena. 611 1

Vanadate, the +5 oxidation state of vanadium, present in mammalian tissues, even in nerve tissue, and a competitive inhibitor of NaK-ATPase, significantly enhanced the release of [3H]noradrenaline evoked from rabbit isolated perfused pulmonary artery by electrical stimulation. Its effect proved to be concentration-dependent. Noradrenaline (10(-6) M) reduced the vanadate-potentiated release of [3H]noradrenaline. The effect of noradrenaline is mediated via alpha 2-adrenoceptors as evidenced by the finding that yohimbine 3 x 10(-7) M prevented its action. The effect of vanadate was dependent on external K ions. When the effect of vanadate on [3H]noradrenaline release was studied under conditions when the NaK-ATPase enzyme activity was inhibited by removal of external K for 45 min, vanadate was ineffective. This finding indicates that the effect is related to the inhibition of NaK-ATPase activity, a condition known to result in transmitter release.
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PMID:Stimulation by vanadate of [3H]noradrenaline release from rabbit pulmonary artery and its inhibition by noradrenaline. 612 38

Red blood cell Na+, K+-, Mg2+-, and Ca2+-adenosine triphosphatase (ATPase) activities were studied longitudinally in eight patients with affective disorders and 12 healthy volunteers. The patients had a higher mean Ca2+-ATPase activity than the volunteers, and the fluctuations in all three ATPase activities were greater in the patients than in the volunteers. Even though the mean Ca2+-ATPase activity was higher during manias and euthymic periods than during depressions, mood and ATPase activities did not correlate with each other in all patients. Lithium carbonate treatment did not alter the ATPase activities, and the quantity of vanadium present in the membranes could not account for the variations in the enzyme activities observed. We suggest that either the RBCs of manic-depressive patients are very sensitive to fluctuations of a lipophilic ATPase activity--regulating factor present in plasma or the patients have at times high levels of such a factor. In some patients, the level of this hypothesized regulator may fluctuate in synchrony with mood changes.
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PMID:RBC membrane adenosine triphosphatase activities in patients with major affective disorders. 613 2

Vanadyl (VO2+) is a potent inductor of the lipid peroxidation in brain microsomes. This effect, however, is obtained at concentrations by two orders of magnitude higher (10(-4)-10(-3)M) than those which effectively inhibit the brain microsomal Na,K-ATPase. At 10(-6)M VO2+ which inhibits 50% of the Na,K-ATPase activity there is no measurable malonyldialdehyde production. Vanadate (VO-3) which is an equally potent inhibitor of Na,K-ATPase as VO2+ has almost no capacity to induce the lipoperoxidation. The addition of 10(-4)M ascorbate to the brain microsomes stimulates the lipoperoxidation to the maximum level regardless of the presence or absence of exogenous vanadium ions. Ascorbate-induced inhibition of brain Na,K-ATPase which is known to be associated with lipoperoxidation is strictly additive with the vanadyl (VO2+) inhibition of this enzyme. Even at submaximal concentrations there is no indication for any potentiation between these two inhibitory systems. The disparity between the mechanisms of ascorbate and vanadyl-induced inhibition of Na,K-ATPase is also documented by the effect of EDTA which inhibits the former type only. It is concluded, that the vanadium-induced inhibition of brain microsomal Na,K-ATPase is not related to induction of lipoperoxidative capacity of the brain.
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PMID:Vanadyl (VO2+) induced lipoperoxidation in the brain microsomal fraction is not related to VO2+ inhibition of Na,K-ATPase. 614 42

The effect of vanadium chloride on rat brain synaptosomal adenosinetriphosphatase (ATPase) activities was determined in vitro and in rats treated at 1 mg/kg.d ip and 10 mg/kg.d po for 10 d. Additional experiments were conducted to determine the effect of vanadium chloride on binding of [3H] ouabain and 45Ca to rat brain synaptosomes. Na+ + K+ - and Ca2+-ATPase activities were inhibited significantly in a concentration-dependent manner by V in vitro. Mg2+ -ATPase inhibition was neither dose-dependent nor significant except at 10(-5) M. Na+ + K+ -ATPase inhibition by V was more pronounced than that of other ATPases studied. Vanadium inhibited [3H] ouabain binding to synaptosomes by 90% at 10(-3) M; the inhibition was concentration-dependent. Binding of 45Ca was inhibited 50% at 10(-4) M; but concentration-dependent inhibition was not evident. Rats treated with vanadium chloride neither became myotonic nor showed any changes in ATPase activities or binding of [3H] ouabain and 45Ca to brain synaptosomes. Lineweaver-Burke plots of the in vitro inhibition of Na+ + K+ -ATPase and [3H] ouabain binding revealed that (1) Na+ + K+ -ATPase activation by ATP was inhibited by V with an increase in Km and a decrease in Vmax; (2) Na+ activation was inhibited noncompetitively by V, as evidenced by a decrease in Vmax and no change in Km; (3)K+ activation was inhibited by V with a decrease in both Vmax and Km; (4) noncompetitive inhibition of Mg2+ -ATPase by V was observed; and (5) the kinetic behavior of [3H] ouabain binding inhibition by V with respect to ATP and Na+ activation was mixed and noncompetitive, respectively. These results suggest that V is a potent inhibitor of Na+ + K+ -ATPase activity in rat brain synaptosomes.
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PMID:Effects of vanadium on different adenosinetriphosphatases and binding of 3H-labeled ouabain and calcium-45 to rat brain synaptosomes. 621 91

The effect of l-noradrenaline and vanadate on the activity of Na+K+-activated ATPase was studied on synaptosomal brain cortex preparation. Using neutron activation analysis it was found that the rat cerebral cortex synaptosomal preparation contains 0.16 microM vanadium. The concentration of vanadium needed to reduce enzyme activity by 50% proved to be 2 x 10(-6) M. Evidence has been provided that the increase by noradrenaline of enzyme activity in synaptosomal preparation depends on the presence of an inhibitory contaminant in commercial ATP preparations. In homogenate, however, noradrenaline was able to enhance enzyme activity even when vanadium-free ATP was used. This fact indicates that noradrenaline removes the inhibitory effect of cytoplasmic factor thereby stimulating enzyme activity.
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PMID:Effect of noradrenaline and vanadium on Na+K+-activated ATPase in rat cerebral cortex synaptosomal preparation. 624 59

The mechanism by which cells reduce cytoplasmic vanadium(V) (vanadate) to vanadium(IV) was investigated using the human red cell as a model system. Vanadate uptake by red cells occurs with a rapid phase involving chemical equilibration across the plasma membrane and a slower phase resulting in a high concentration of bound vanadium(IV). The slow phase was inhibited in glucose-starved cells and restored upon addition of glucose indicating an energy requirement for this process. The time course of vanadium(IV) appearance (monitored by EPR spectroscopy of intact cells) paralleled the slow phase of uptake indicating that this phase involves vanadium reduction. The reduction of intracellular vanadate to vanadium(IV) was nearly quantitative after 23 h. The intracellular reduction is not enzymatic, since a similar time course of vanadium reduction and binding to hemoglobin was observed when glutathione was added to a hemoglobin + vanadate solution in vitro. Vanadium(IV) binding to hemoglobin was reduced by addition of ATP, 2,3-diphosphoglycerate or EDTA, probably through chelation of the cation. The stability constant of the ATP-vanadium (IV) complex was determined to be 150 M-1 at pH 4.9. The time course of red cell vanadate uptake and reduction was followed in the concentration range in which approximately 60% inhibition of the (Na+ + K+)-ATPase is observed. It is concluded that vanadate is reduced by cytoplasmic glutathione in this concentration range and that the reduction explains the resistance of the (Na+ + K+)-ATPase to vanadium in intact cells.
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PMID:Glutathione reduces cytoplasmic vanadate. Mechanism and physiological implications. 624 16


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