Characterization of the Neutralizing Activity of Digoxin-Specific Fab toward Ouabain-Like Steroids
Characterization of the Neutralizing Activity of Digoxin-Specific Fab toward Ouabain-Like Steroids
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地高辛特异性 Fab 对哇巴因样类固醇的中和活性的表征
DOI：
10.1124/jpet.104.065250
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发表时间：
2004
影响因子：
3.5
通讯作者：
R. Edwards
中科院分区：
文献类型：
--
作者：
M. Pullen;D. Brooks;R. Edwards
地高辛特异性Fab（Digibind）是从绵羊血清制备的抗地高辛Fab片段的混合物，并且用作地高辛中毒的治疗。地高辛特异性Fab已显示在大鼠和人类中中和内源性Na+/K+ ATP酶抑制剂（内源性地高辛样Na+/K+ ATP酶调节因子; EDLF）并降低血压。虽然EDLF的确切结构尚不清楚，但在哺乳动物血浆中已检测到与哇巴因、蟾蜍灵和海蟾毒配基相同或结构相关的化合物。在这项研究中，EDLF的一些结构特征推断从地高辛特异性Fab的能力，以中和几个已知的强心内酯和蟾蜍二烯内酯的Na+/K+ ATP酶抑制活性。从[3 H]哇巴因结合和酶联免疫吸附测定实验中获得了额外的结构信息。地高辛特异性Fab具有在一定程度上与所有测试的强心内酯和蟾蜍二烯内酯相互作用的能力。然而，地高辛特异性Fab在中和哇巴因和蟾蜍灵方面比海蟾毒配基强20倍以上。因此，在先兆子痫和高血压动物模型中观察到的地高辛特异性Fab的抗高血压作用可能是由于与哇巴因或蟾蜍灵相同或结构相似的分子。
Digoxin-specific Fab (Digibind) is a mixture of antidigoxin Fab fragments prepared from sheep sera and is used as a treatment for digoxin poisoning. Digoxin-specific Fab has been shown to neutralize an endogenous Na+/K+ ATPase inhibitor (endogenous digoxin-like Na+/K+ ATPase regulatory factor; EDLF) in rats and humans and to lower blood pressure. Although the exact structure of EDLF is unknown, compounds identical to or structurally related to ouabain, bufalin, and marinobufagenin have been detected in mammalian plasma. In this study, some structural characteristics of EDLF were inferred from the ability of digoxin-specific Fab to neutralize the Na+/K+ ATPase inhibitory activity of several known cardenolides and bufodienolides. Additional structural information was obtained from [3H]ouabain binding and enzyme-linked immunosorbent assay experiments. Digoxin-specific Fab had the ability to interact to some extent with all of the cardenolides and bufodienolides tested. However, digoxin-specific Fab was more than 20-fold more potent in neutralizing ouabain and bufalin than marinobufagenin. The antihypertensive effect of digoxin-specific Fab seen in preeclampsia and animal models of hypertension may therefore be due to a molecule identical to or structurally similar to ouabain or bufalin.
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影响因子：
3.2
作者：
Graves,SW;Lincoln,K;Cook,SL;Seely,EW
通讯作者：
Seely,EW
使用新型哇巴因亲和柱纯化活性 Na -K -ATP 酶。
DOI：
10.1152/ajpcell.1998.275.4.c1167
发表时间：
1998
期刊：
The American journal of physiology
影响因子：
--
作者：
Yingst,DR;Yang,SY;Schiebinger,R
通讯作者：
Schiebinger,R
影响因子：
8.3
作者：
O. Fedorova;N. I. Kolodkin;N. Agalakova;E. Lakatta;A. Bagrov
通讯作者：
O. Fedorova;N. I. Kolodkin;N. Agalakova;E. Lakatta;A. Bagrov
影响因子：
7.3
作者：
Farr, CD;Tabet, MR;Welsh, WJ
通讯作者：
Welsh, WJ
影响因子：
9.3
作者：
M. A. El-Masri;B. Clark;H. Qazzaz;R. Valdes
通讯作者：
M. A. El-Masri;B. Clark;H. Qazzaz;R. Valdes