Dose-dependent reversal of digoxin-inhibited activity of an in vitro Na(+)K(+)ATPase model by digoxin-specific antibody
Dose-dependent reversal of digoxin-inhibited activity of an in vitro Na(+)K(+)ATPase model by digoxin-specific antibody
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DOI：
10.1016/0378-4274(96)03647-8
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发表时间：
1996-05-01
影响因子：
3.5
通讯作者：
Scherrmann, JMG
中科院分区：
文献类型：
--
作者：
Cano, NJ;Sabouraud, AE;Scherrmann, JMG
我们根据（a）Na（+）K（+）ATP酶的初始抑制程度和（B）抗体的中和剂量，研究了地高辛特异性Fab B片段逆转地高辛诱导的大鼠脑微粒体Na（+）K（+）ATP酶抑制的效力。地高辛浓度-Na（+）K（+）ATP酶抑制曲线的数学分析支持存在2种地高辛敏感性Na（+）K（+）ATP酶亚型。低（α 1）和高（α 2）地高辛亲和力同工酶的IC 50分别为1.3 x 10（-4）M和2.5 x 10（-8）M。地高辛诱导的Na（+）K（+）ATP酶抑制的逆转依赖于地高辛特异性Fab的浓度。当Fab：地高辛比例为化学计量时观察到最大效应，并且在研究的4种地高辛浓度下添加过量抗体不会导致抑制完全逆转。这种简单快速的体外模型将是预测新一代抗体疗效的有用工具。
We investigated the potency of digoxin-specific Fab fragments to reverse digoxin-induced Na(+)K(+)ATPase inhibition in rat brain microsomes according to (a) the extent of initial inhibition of Na(+)K(+)ATPase and (b) the neutralizing dose of antibody. Mathematical analysis of the digoxin concentration-Na(+)K(+)ATPase inhibition curve supports the existence of 2 digoxin sensitive Na(+)K(+)ATPase isoforms. The IC50 was 1.3 x 10(-4) M and 2.5 x 10(-8) M for the low (alpha 1) and high (alpha 2) digoxin affinity isoenzyme, respectively. The reversal of digoxin-induced Na(+)K(+)ATPase inhibition was dependent on the digoxin-specific Fab concentration. The maximal effect was observed when the Fab:digoxin ratio was stoichiometrical and addition of an excess of antibodies did not result in a complete reversal of inhibition at the 4 digoxin concentrations studied. This simple and rapid in vitro model will be a useful tool to predict the efficacy of a new generation of antibodies.