不同亲脂性洋地黄磺酸盐衍生物对钠钾ATP酶的活性位点定向烷基化作用

Active site-directed alkylation of Na+-K+-ATPase by digitalis sulphonate derivatives of different lipophilicity.

作者信息

Fricke U, Klaus W, Rogatti M

出版信息

Br J Pharmacol. 1981 Jan;72(1):25-9. doi: 10.1111/j.1476-5381.1981.tb09100.x.

DOI:10.1111/j.1476-5381.1981.tb09100.x

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2071539/

Abstract

1 Sulphonate derivatives of k-strophanthidin and digitoxigenin were tested as active site-directed labels of Na+-K+-adenosine triphosphatase (Na+-ATPase) from guinea-pig heart. 2 Lipophilicity ranged between P = 93 for strophanthidin-3-tosyloxy-acetate (STA) and P = 3028 for digitoxigenin-3-tosyloxy-acetate (DTA). 3 Although the alkylating moiety of STA and DTA was identical, the reversibility of Na+-K+-ATPase inhibition varied appreciably (82% and 35% respectively). 4 It is concluded that lipophilicity contributes considerably to the irreversible binding of alkylating cardiotonic steroids to myocardial Na+-K+-ATPase.

摘要

1 将毒毛花苷元（k-毒毛旋花子苷元）和洋地黄毒苷元的磺酸盐衍生物作为豚鼠心脏钠钾-腺苷三磷酸酶（Na+-ATP酶）活性位点导向标记物进行了测试。2 亲脂性范围为毒毛花苷元-3-对甲苯磺酸氧基乙酸酯（STA）的P = 93至洋地黄毒苷元-3-对甲苯磺酸氧基乙酸酯（DTA）的P = 3028。3 尽管STA和DTA的烷基化部分相同，但Na+-K+-ATP酶抑制的可逆性有明显差异（分别为82%和35%）。4 得出的结论是，亲脂性对烷基化强心甾类与心肌Na+-K+-ATP酶的不可逆结合有很大贡献。

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Br J Pharmacol. 1981 Jan;72(1):25-9. doi: 10.1111/j.1476-5381.1981.tb09100.x.

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本文引用的文献

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A new, sensitive determination of phosphate.一种新的、灵敏的磷酸盐测定方法。

Anal Biochem. 1969 Jul;30(1):51-7. doi: 10.1016/0003-2697(69)90372-8.

2

Evidence for a dissociation between positive inotropic effect and inhibition of the Na+-K+-ATPase by ouabain, cassaine and their alkylating derivatives.哇巴因、毒毛旋花子苷及其烷基化衍生物对心肌正性肌力作用与钠钾-ATP酶抑制作用之间解离的证据。

Eur J Pharmacol. 1974 May;26(2):166-74. doi: 10.1016/0014-2999(74)90223-4.

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Photoaffinity labeling of the ouabain-binding site on (Na+ plus K+) adenosinetriphosphatase.（钠钾）三磷酸腺苷酶上哇巴因结合位点的光亲和标记

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A simple preparation technique for a microsomal Maplus-K-plus-activated ATPase from cardiac tissues of different species.

Prep Biochem. 1974;4(1):13-29. doi: 10.1080/00327487408068183.

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Dissociation of the positive inotropic action of digitalis from inhibition of sodium- and potassium-activated adenosine triphosphate.洋地黄正性肌力作用与钠钾激活三磷酸腺苷抑制作用的解离。

J Pharmacol Exp Ther. 1973 Apr;185(1):1-11.

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Structue-activity relationships of cardiotonic steroids for the inhibition of sodium- and potassium-dependent adenosine triphosphatase. I. Dissociation rate constants of various enzyme-cardiac glycoside complexes formed in the presence of magnesium and phosphate.

Mol Pharmacol. 1973 Jan;9(1):51-60.

7

Membrane adenosine triphosphatase. The effect of potassium on the formation and dissociation of the ouabain-enzyme complex.

J Pharmacol Exp Ther. 1971 Mar;176(3):545-57.

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Inhibition of sodium- and potassium-dependent adenosine triphosphatase by cardenolide alkylating agents.强心甾烷基化剂对钠钾依赖型三磷酸腺苷酶的抑制作用。

J Med Chem. 1971 Jun;14(6):509-11. doi: 10.1021/jm00288a011.

9

On the reversibility of binding of cardiotonic steroids to a partially purified (Na+K)-activated adenosinetriphosphatase from beef brain.

Biochem Biophys Res Commun. 1970 Aug 24;40(4):880-6. doi: 10.1016/0006-291x(70)90985-x.

10

[Liability of different cardenolides on papillary muscle and on microsomal ATPase of guinea pig hearts].[不同强心甾对豚鼠心脏乳头肌和微粒体ATP酶的作用]

Naunyn Schmiedebergs Arch Pharmakol. 1971;268(2):200-9.

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