[哺乳动物木脂素：可能参与内源性洋地黄活性]

[Mammalian lignans: possible involvement in endogenous digitalis activity].

作者信息

Braquet P, Senn N, Fagoo M, Garay R, Robin J P, Esanu A, Chabrier E, Godfrain T

出版信息

C R Acad Sci III. 1986;302(12):443-8.

Abstract

Lignans are natural products, some of which were recently discovered in animal urines, semen and blood plasma. We investigated the actions of animal lignans obtained by total synthesis or extracted from urines of pregnant women on Na+, K+-ATPase in human red cells and human and guinea-pig heart cell membranes. Some of the tested lignans (enterolactone, prestegane B and 3-O-methyl enterolactone) inhibited Na+, K+-pump activity in human red cells with IC50 ranging from 5 to 9 X 10(-4) M. The IC50 for ouabain (7 X 10(-7) M) was not modified by addition of lignans. Enterolactone inhibited Na+, K+-ATPase activity in human and guinea pig heart membranes. It also displaced [3H]-ouabain binding from human heart with IC50 = 1.5 X 10(-4) M. The apparent dissociation rate constants (kd) of [3H]-ouabain were not different in presence of digoxin or enterolactone. Enterolactone exhibited a poor cross reactivity against antidigoxin antibodies. The aglycones of the lignans studied here were slight inhibitors of the Na+, K+-ATPase. However, we cannot exclude that a glycosyl- (and/or butenolide-) derivative of enterolactone could be one "endogenous ouabain-like" factor.

摘要

木脂素是天然产物，其中一些最近在动物尿液、精液和血浆中被发现。我们研究了通过全合成获得或从孕妇尿液中提取的动物木脂素对人红细胞以及人和豚鼠心肌细胞膜上Na⁺、K⁺-ATP酶的作用。一些受试木脂素（肠内酯、前孕二烯酮B和3 - O - 甲基肠内酯）抑制人红细胞中的Na⁺、K⁺-泵活性，IC50范围为5至9×10⁻⁴ M。哇巴因（7×10⁻⁷ M）的IC50不会因添加木脂素而改变。肠内酯抑制人和豚鼠心肌膜中的Na⁺、K⁺-ATP酶活性。它还以IC50 = 1.5×10⁻⁴ M的浓度从人心脏中取代[³H] - 哇巴因结合。在存在地高辛或肠内酯的情况下，[³H] - 哇巴因的表观解离速率常数（kd）没有差异。肠内酯与抗地高辛抗体的交叉反应性较差。本文研究的木脂素苷元是Na⁺、K⁺-ATP酶的轻度抑制剂。然而，我们不能排除肠内酯的糖基 - （和/或丁烯内酯 - ）衍生物可能是一种“内源性哇巴因样”因子。