Inhibition of the Na,K-ATPase by the antiarrhythmic drug, Bretylium.
Inhibition of the Na,K-ATPase by the antiarrhythmic drug, Bretylium.
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抗心律失常药物 Bretylium 抑制 Na,K-ATP 酶。
DOI：
10.1111/j.1749-6632.2003.tb07265.x
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发表时间：
2003
影响因子：
5.2
通讯作者：
Milanick,MarkA
中科院分区：
文献类型：
--
作者：
Gatto,Craig;Barkulis,CTheodore;Schneider,WilliamR;Holden,JeremyP;Arnett,KristaL;Milanick,MarkA
溴苄铵（BrT）是一种广泛用作钾通道阻滞剂的季胺。1在此，我们报告BrT也抑制Na，K-ATP酶; BrT IC 50值（在20 mM K+下）约为5 mM。有趣的是，酶活性对BrT的反应遵循双相模式;最初，BrT刺激Na，K-ATP酶（[BrT]≤ 1 mM），随后产生抑制作用。本文仅讨论BrT对Na，K-ATP酶的抑制作用，随着K（或Rb）浓度的增加，BrT对Na，K-ATP酶活性的抑制作用消失，而ATP酶的最大活性速率不变。相反，增加Na浓度无法与BrT竞争，Vmax显著降低。这些观察结果与BrT抑制豚鼠心脏Na，K-ATP酶的报告一致。2我们观察到50 mM BrT（即ATP酶IC 50的10倍）不能阻止Na和MgATP形成Eap。[3]这些观察结果以及K竞争表明，BrT（一种阳离子）通过与E2-p结合来抑制Na泵。基于这一点和以前的工作，BrT似乎通过阻止细胞外K结合来抑制Na泵。3
Bretylium (BrT) is a quaternary amine used extensively as a potassium channel blocker. 1 Here, we report that BrT also inhibits the Na, K-ATpase; the BrT IC50 value (at 20 mM K+) was approximately 5 mM. Interestingly, enzyme activity followed a biphasic pattern in response to BrT; initially, BrT stimulated Na, K-ATpase ([BrT]≤ 1 mM), followed by an inhibitory effect. We limit our discussion to BrT inhibition of the Na, K-ATpase.Increasing concentrations of K (or Rb) were able to overcome the inhibitory effect of BrT, and the maximal velocity for ATpase activity was unchanged. In contrast, increasing Na concentration was unable to compete with BrT and Vmax was significantly reduced. These observations are in line with reports of BrT inhibition of guinea pig cardiac Na, K-ATpase. 2 We observed that 50 mM BrT (ie, 10 times the IC50 for ATpase) was unable to prevent the formation of Eap from Na and MgATp. 3 These observations, together with K competition, suggest that BrT, a cation, inhibits the Na pump by binding to E2-p. Based on this and previous work, it appears that BrT inhibits the Na pump by preventing extracelluar K binding. 3
DOI：
10.1073/pnas.090492697
发表时间：
2000-05-23
影响因子：
11.1
作者：
Garfinkel, A;Kim, YH;Chen, PS
通讯作者：
Chen, PS
甲苯磺酸溴节铵与豚鼠心肌 Na( )-K( )-ATP 酶的相互作用。
DOI：
10.1016/0306-3623(91)90233-v
发表时间：
1991
期刊：
General pharmacology
影响因子：
--
作者：
N. Dzimiri;A. Almotrefi
通讯作者：
A. Almotrefi