羟基孕酮衍生物的哇巴因受体结合
Ouabain receptor binding of hydroxyprogesterone derivatives.
作者信息
Chow E, Kim R S, Labella F S, Queen G
出版信息
Br J Pharmacol. 1979 Nov;67(3):345-52. doi: 10.1111/j.1476-5381.1979.tb08686.x.
Abstract
1 A specific and sensitive radioreceptor assay ahs been devised which is based on high affinity, saturable binding of 9 nM [3H]-ouabain to the total particulate fraction isolated from dog heart. Ouabain and other cardiac glycosides, including the aglycones, were about equipotent in their ability to displace [3H]-ouabain from its receptor, the IC50s ranging from 10 to 30 nM. 2 The only other substances found to compete significantly in the assay were derivatives of hydroxyprogesterone having a 17 alpha-acetate substituent: chlormadinone acetate, megestrol acetate, cyproterone acetate and medroxyprogesterone acetate, with IC50s of 2, 7.4, 9 and 21 microM, respectively. Prednisolone-3,20-bisguanyl-hydrazone, reported to have inotropic activity, gave an IC50 of 6.4 microM. Cyproterone-17 alpha-OH was less active (IC50 90 microM) than cyproterone-17 alpha-acetate. 3 A large number of peptide and protein hormones, steroid hormones and their metabolites, amines, and drugs were inactive.
摘要
- 已设计出一种特异性和敏感性高的放射受体测定法，该方法基于9 nM [3H]哇巴因与从犬心脏分离出的总微粒体部分的高亲和力、可饱和结合。哇巴因和其他强心苷，包括苷元，在将[3H]哇巴因从其受体上置换下来的能力方面大致相当，半数抑制浓度（IC50）范围为10至30 nM。2. 在该测定中发现的唯一其他有显著竞争作用的物质是具有17α - 醋酸酯取代基的羟孕酮衍生物：醋酸氯地孕酮、醋酸甲地孕酮、醋酸环丙孕酮和醋酸甲羟孕酮，其IC50分别为2、7.4、9和21 μM。据报道具有变力活性的泼尼松龙 - 3,20 - 双胍腙的IC50为6.4 μM。环丙孕酮 - 17α - OH的活性（IC50为90 μM）低于环丙孕酮 - 17α - 醋酸酯。3. 大量的肽和蛋白质激素、甾体激素及其代谢产物、胺类和药物均无活性。
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引用本文的文献
1
14 beta-Hydroxyprogesterone binds to the digitalis receptor, inhibits the sodium pump and enhances cardiac contractility.14β-羟基孕酮与洋地黄受体结合，抑制钠泵并增强心肌收缩力。
Br J Pharmacol. 1988 Feb;93(2):453-61. doi: 10.1111/j.1476-5381.1988.tb11453.x.
本文引用的文献
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ENZYMATIC BASIS FOR ACTIVE TRANSPORT OF NA+ AND K+ ACROSS CELL MEMBRANE.钠离子和钾离子跨细胞膜主动运输的酶学基础
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Effects of cations on ouabain binding by intact human erythrocytes.阳离子对完整人红细胞哇巴因结合的影响。
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Ouabain binding and cation transport in human erythrocytes.哇巴因与人红细胞中的结合及阳离子转运
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Cardiac glucosides: correlations among Na+ K+-ATPase, sodium pump and contractility in the guinea pig heart.强心苷：豚鼠心脏中钠钾ATP酶、钠泵与收缩性之间的相关性
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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。
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Biochim Biophys Acta. 1973 Dec 22;330(3):302-15. doi: 10.1016/0005-2736(73)90235-6.
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