• 약학회지
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• 제46권6호
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• pp.441-447
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• 2002

It has been well known that vanadium shows various physiological and pharmacological properties such as an insulin-mimetic effect. In view of the reported toxic effects there is the problems that the safety margin is narrow because of its strong toxicity, Vanadate was tested for its ability to cause blood aggregation. Although vanadate or $H_2O$$_2$ alone had little effect on platelet aggregation, treatment of vanadate and $H_2O$$_2$ together induced platelet aggregation indicated that it was occurred by pervandate or hydroxyl radical produced from the reaction of vanadate and $H_2O$$_2$. It was dependent on extracellular $Ca^{2+}$ion. Platelet aggregation caused by vanadate and $H_2O$$_2$ was inhibited by ascorbic acid, tocopherol, catalase, mannitol, and Tiron. In contrast to vanadate, vanadium yeast prepared by uptaking vanadate in yeast cells did not induce platelet aggregation in the presence of $H_2O$$_2$.>.

• The Korean Journal of Physiology
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• 제18권2호
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• pp.125-137
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• 1984

Vanadate의 수축에 이용되는 $Ca^{2+}$의 동원 경로와 Na-Pump억제가 vanadate의 수축에 어떤 영향을 미치는 지를 밝히기 위해 본 실험을 시행하여 다음과 같은 곁과를 얻었다. 1) 흰쥐의 자궁근에서는 vanadate는 수축을 일으켜 $5{\times}10^{-4}M$에서 최대수축을 나타내었으며 사람의 자궁근이 흰쥐의 자중근에 비해 vanadate에 더 민감한 반응을 보였다. 2) Vanadate에 의한 수축은 $Ca^{2+}$제거에 의해 완전히 억제되지 않았고 사람의 자궁근이 외부 $Ca^{2+}$의 농도변화에 더 민감한 반응을 보였다. 3) Vanadate에 의한 수축은 verapamil농도를 증가시킴에 따 억제되었으며 100k에 극한 수축을 완전 억제시키는$3{\times}10^{-5}M$ verapamil 존재하에서도 최대수의 40%정도가 남아있었고, 이 크기는 $Ca^{2+}$없는 용액에서의 수축의 크기와 유사하였다. 4) Na-pump억제시 vanadate의 수축은 증가하였고 이 현상은 $3{\times}10^{-5}M$ verapamil 존재하에서도 나타났다. 5) $Ca^{2+}$없는 ouabain용액에서 전처치후에 vanadate에 의한 수축은 증가하지 않았으나 외부내 $Ca^{2+}$을 부가할 나타나는 반음은 대조군에 비해 현저히 증가하였다. 6) Verapamil 존재시 vanadate에 의한 $Ca^{45}$유입은 완전히 억제되었으나 ouabain으로 처리한 후는 verapamil 존재하에서도 vanadate가 현저히 $Ca^{45}$유입을 일으켰다. 7) Ouabain이나 K 없는 용액으로 치리시간이 증가함에 따라 vanadate에 의한 수축의 증가정도는 더욱 더 현저하였다. 8) Ouabain 전처치시 증가된 vanadate에 의한 수축은 $10^{-4}M$ papaverine에 의해 현저히 억제되었다. 9) Acetylcholine에 의한 수축은 verapamil 존재하에서도 Na-pump억제 시간이 증가함에 따라 증가하였다. 이상의 결과로 볼 때 vanadate에 대해 사람의 자궁근이 흰쥐의 자궁근에 비해 더 민감한 반응을 보이고 vanadate에 의한 수축에는 외부와 내부 $Ca^{2+}$이 모두 이용되며 Na-pump 억제시 여러가지 근수축물질이 verapamil에 의해 억제되지 않는 $Ca^{2+}$유입을 일으키며 이 유입경로의 성질은 확실히 알 수 없으나 Papaverine에 의해 억제되며 막전위의 변화와 관련이 있는 것으로 생각된다.

• The Korean Journal of Physiology
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• 제18권2호
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• pp.139-150
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• 1984

Vanadate의 회장 평활근에 대한 수축작용이 Na-K-ATPase를 억제하기 때문인지를 구명하기 위하여 Na-K-ATPase를 억제하는 ouabain과의 작용의 차이를 관찰한 결과 다음과 같은 결론을 얻었다. 1) Ouabain에 의해 나타나는 수축은 2중 peak를 나타내었으나 vanadate 의해서는 단일 Peak만을 보였다. 2) Ouabain에 의한 수축은 atropine$(2{\times]10^{-6}M)$에 의해 강력하게 억제되었으나 vanadate의 작용은 영향을 받지 않았다. 3) Ouabain에 의한 수축은 vanadate에 비해 외부의 $Ca^{++}4농도 및 Ca-길항제에 대해 민감하게 영향을 받았다. 4) 용액내 $Na^+$이 없을때 혹은 고농도의 $K^+$존재하에서 ouabain에 의한 수축반응은 거의 나타나지 않았으나 vanadate에 의한 수축은 영향을 받지 않았다. 5) Vanadate에 의한 수축은 ouabain 존재시에 더욱 증가되었다. 6) 3시간동안 incubation한 결과 vanadate는 ouabain과 달리 세포내 $Na^+$의 농도에 영향을 미치지 못하였다. 이상의 결과로 보아 ouabain과 vanadate는 서로 다른 기전에 의해 회장 평활근에서 수축반응을 유발시키는 것으로 추측된다.

• The Korean Journal of Physiology
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• 제17권2호
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• pp.161-168
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• 1983

Studies on the effects of vanadate for Na-K-ATPase activity were carried out with rabbit renal cortex. 1) Na-K-ATPase activity was inhibited with the concentrations of vanadate in incubation medium. The vanadate concentration at which activity was inhibited by 50%$(ID_{50})$ was $10^{-6}M$ and Hill coefficient was 1.00. 2) The fractional inhibition by constant concentration of vanadate decreased with increasing enzyme concentration. 3) Increasing $K^+$ and $Na^+$ concentrations in incubation medium diminished the ability to inhibit Na-K-ATPase by vanadate whereas increasing $K^+$ and $Mg^{2+}$ concentrations potentiated the inhibition of Na-K-ATPase by vanadate. 4) Vanadate didn't inhibit Na-K-ATPase at pH 6.6. Increasing pH potentiated the inhibition of Na-K-ATPase activity. 5) Vanadate inhibited Na-K-ATPase activity reversibly in all range of concentrations in dilution experiment. These results show that vanadate inhibits Na-K-ATPase activity with interacting at $KE_2$ state reversibly.

• The Korean Journal of Physiology
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• 제17권2호
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• pp.143-159
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• 1983

Vanadate가 가토 신피질절편에서 PAH이동과 Na-K-ATPase활성에 미치는 효과를 관찰한 결과 다음과 같은 결론을 얻었다. 1) Vanadate는 Na-K-ATPase활성을 농도에 따라 억제하였으며 $7.94{\times}10^{-7}M$에서 이 효소의 활성이 50% 억제되었다. 2) Vanadate는 PAH의 능동적이동을 농도에 따라 억제하였으며 50%억제농도는 대략 $10^{-4}M$ 이었고, 수동적이동에는 영향을 미치지 못하였다. 조직내 Na과 K의 양도 vanadate가 PAH이동을 억제하는 농도 범위에서 같이 변화하였고 산소소모량은 $10^{-4}M$까지는 약간 감소하였으나 $10^{-3}M$에서는 오히려 증가하였다. 3) 30분간 preincubation한 후에도 15분까지의 PAH이동은 30분 이후에 비해 vanadate에 의해 적게 억제되었다. 4) $10^{-4}M$ vanadate와 $10^{-4}M$ ouabain은 가역적으로 PAH 이동을 억제하였으며 $10^{-3}M$ vanadate는 비가역적으로 억제하였고 장시간 세척후에도 거의 같은 정도의 억제양상을 나타내었다. 5) Vanadate에 의한 PAH이동의 억제정도는 incubation용액내 $Na^+$의 감소, $K^+$의 증가에 의하여 증가하였고 $Ca^{2+}$의 농도 변화에 의해서는 영향을 받지 않았다. 6) Vanadate가 존재치 않을 때 Tris완충용액 사용시는 pH 8.2까지 PAH축적정도가 증가하였고 phosphate완충용액 사용시는 pH 7.4에서 최대축적치를 보였다. pH가 증가함에 따라 억제정도는 증가하였으며 같은 pH에서도 완충용액의 종류에 따라 vanadate에 의한 억제정도가 달랐다. 7) Vanadate와 ouabain은 PAH이등과 Na-K-ATPase활성에 부가적 억제작용을 나타내었다. 이상의 결과로 vanadate는 가토신장의 세포내부에서 Na-K-ATPase를 가역적으로 억제함으로써 PAH의 이동을 억제하는 것으로 생각되며 PAH의 이동은 Na-K-ATPase활성과 기능적으로 밀접히 연결되어 있는 것으로 생각된다.

• Archives of Pharmacal Research
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• 제21권3호
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• pp.315-319
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• 1998

Gastric smooth muscle of cats was used to investigate the involvement of protein kinase in vanadate-induced contraction. Vanadate caused a contraction of cat gastric smooth muscle in a dose-dependent manner. Vanadate-induced contraction was totally inhibited by 2 mM EGTA and 1.5 mM $LACI_3$ and significantly inhibited by $10\mu$M verapamil and $1\mu$M nifedipine, suggesting that vanadate-induced contraction is dependent on the extracellular $Ca^{2+}$ concentration, and the influx of extracellular $Ca^{2+}$ was mediated through voltage-dependent $Ca^{2+}$ channel. Both protein kinase C inhibitor and tyrosine kinase inhibitor significantly inhibited the vanadate-induced contraction and the combined inhibitory effect of two protein kinase inhibitors was greater than that of each one. But calmodulin antagonists did not have any influence on the vanadate-induced contraction. On the other hand, both forskolin ($1\mu$M) and sodium nitroprusside ($1\mu$M) significantly inhibited vanadate-induced contraction. Therefore, these results suggest that both protein kinase C and tyrosino kinase are involved in the vanadate-induced contraction which required the influx of extracellular $Ca^{2+}$ in cat gastric smooth muscle, and that the contractile mechanism of vanadate may be different from that of agonist binding to its specific receptor.

• The Korean Journal of Physiology
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• 제20권2호
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• pp.175-183
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• 1986

Since it was proposed that vanadate may be an ‘ideal endogenous regulator of the $Na^+,\;K^+-ATPase$ activity (Cantley et at, 1979), vanadate has been a subject of intensive research and a variety of its physiological effects have been described (Nechay, 1984). In isolated guinea pig heart muscle vanadate shows a positive inotropic effect on ventricular muscle, while it induces a negative inotropic effect on atrial muscle. But its underlying mechanism has not been elucidated so far. Therefore, in this study the flux rates of calcium ion into and from guinea pig heart muscle were measured to throw some light on the underlying mechanism, because those rates have been known to be closely related to the cardiac contractility and the results are summarized as follows: 1) Calcium efflux rates from the intracellular $Ca^{++}$ pool (compartment 4) of both guinea pig left atrium and right ventricle were significantly reduced by vanadate and their pool sizes were significantly increased by vanadate. 2) The magnitude of calcium influx into left atrium was reduced by vanadate, While the magnitude of calcium influx into right ventricle was not affected by vanadate. From these results, it may be concluded that the positive inotropic effect of vanadate on the ventricular muscle was due to a reduced efflux rate of calcium ion and its negative inotropic effect on atrial muscle was resulted from a reduced influx of calcium ion.

• Biomolecules & Therapeutics
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• 제9권4호
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• pp.270-276
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• 2001

Vanadium yeast was prepared by uptaking vanadate in yeast cells. The growth rate of yeast cells was enhanced by 1-5% glucose. While the growth rate of yeast cells was not significantly affected by YEPD containing less than 1mM vanadate, it was completely inhibited by 2.5 mM vanadate. Vanadium uptake in yeast cells was increased with increasing vanadate concentration in growth medium. Vanadate (V) was reduced to vanadyl (IV) in yeast cells associating with macromolecular compounds in cells. Oral administration of vanadium yeast significantly reduced blood glucose levels of streptozotocin treated rats same as vanadate. Vanadate and vanadium yeast similarly increased glucose oxidation in isolated adipocytes. Therefore, it was suggested that vanadium yeast could have an antidiabetic activity potency similar to that of vanadate.

• Toxicological Research
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• 제34권2호
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• pp.143-150
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• 2018

It has been demonstrated that vanadate causes nephrotoxicity. Vanadate inhibits renal sodium potassium adenosine triphosphatase (Na, K-ATPase) activity and this is more pronounced in injured renal tissues. Cardiac cyclic adenosine monophosphate (cAMP) is enhanced by vanadate, while increased cAMP suppresses Na, K-ATPase action in renal tubular cells. There are no in vivo data collectively demonstrating the effect of vanadate on renal cAMP levels; on the abundance of the alpha 1 isoform (${\alpha}_1$) of the Na, K-ATPase protein or its cellular localization; or on renal tissue injury. In this study, rats received a normal saline solution or vanadate (5 mg/kg BW) by intraperitoneal injection for 10 days. Levels of vanadium, cAMP, and malondialdehyde (MDA), a marker of lipid peroxidation were measured in renal tissues. Protein abundance and the localization of renal ${\alpha}_1-Na$, K-ATPase was determined by Western blot and immunohistochemistry, respectively. Renal tissue injury was examined by histological evaluation and renal function was assessed by blood biochemical parameters. Rats treated with vanadate had markedly increased vanadium levels in their plasma, urine, and renal tissues. Vanadate significantly induced renal cAMP and MDA accumulation, whereas the protein level of ${\alpha}_1-Na$, K-ATPase was suppressed. Vanadate caused renal damage, azotemia, hypokalemia, and hypophosphatemia. Fractional excretions of all studied electrolytes were increased with vanadate administration. These in vivo findings demonstrate that vanadate might suppress renal ${\alpha}_1-Na$, K-ATPase protein functionally by enhancing cAMP and structurally by augmenting lipid peroxidation.

• The Korean Journal of Physiology
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• 제20권2호
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• pp.157-164
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• 1986

Since it has been reported that vanadate inhibits $Ca^{++}-ATPase$ activity without affecting $Ca^{++}$ uptake, this study was undertaken to investigate the effects of vanadate on $Ca^{++}-ATPase$ activity and $Ca^{++}$ uptake in the sarcoplasmic reticulum of rat skeletal muscle. The following results were obtained. 1) $Ca^{++}$ activated ATPase activity of the intact sarcoplasmic reticulum was significantly inhibited when vanadate was added to the incubation medium at concentration greater than $10^{-6}\;M$. However $Mg^{++}$-ATPase activity of the intact SR was not affected by vanadate at concentrations ranging from $10^{-7}\;to\;10^{-4}\;M.$ Similarly, $Ca^{++}-ATPase$ activity in sonicated sarcoplasmic reticulum was significantly reduced by vanadate at a concentration $10^{-7}$ M or higher. 2) The uptake of $Ca^{++}$ by isolated sarcoplasmic reticulum was also inhibited by vanadate under the conditions where the turnover rate of $Ca^{++}-ATPase$ was made to increase. These results suggest that the inhibition of $Ca^{++}$ uptake by vanadate may be correlated with that of $Ca^{++}-ATPase$ if experimental conditions are properly set.