Marinobufagenin interferes with the function of the mineralocorticoid receptor.
Marinobufagenin interferes with the function of the mineralocorticoid receptor.
复制标题
海蟾蜍配基干扰盐皮质激素受体的功能。
DOI：
10.1016/j.bbrc.2007.03.085
复制
发表时间：
2007
影响因子：
3.1
通讯作者：
Puschett,JulesB
中科院分区：
文献类型：
--
作者：
Smith,CarolynL;He,Qiang;Huang,Luping;Foster,Estrella;Puschett,JulesB
华蟾素(MBG)是一种强心类固醇，属于蟾酥二烯内酯类化合物，具有抑制钠/钾-三磷酸腺苷酶的作用，从而导致钠尿。MBG参与体积扩张介导的高血压的发病机制已经有一段时间了，我们已经提出MBG参与了先兆子痫的高血压。我们验证了MBG可能通过促进盐皮质激素受体(MR)的活性而导致这些形式的高血压的假设。然而，我们的数据表明，MBG通过抑制受体的转录活性来干扰MR的功能，这反映在SRC-3共激活子与MR之间的相互作用减少。因此，MBG导致钠尿的能力可能不仅是由于抑制了Na+/K+-ATPase活性，还因为它能够干扰依赖MR的肾脏末端Na/K/H交换器的表达。
Marinobufagenin (MBG) is a cardiotonic steroid of the bufadienolide class of compounds which has the ability to inhibit the ubiquitous enzyme, Na+/K+-ATPase, resulting in natriuresis. The involvement of MBG in the pathogenesis of volume expansion-mediated forms of hypertension has been suggested for some time, and we have proposed that MBG participates in the hypertension noted in preeclampsia. We examined the hypothesis that MBG might contribute to these forms of hypertension by promoting the activity of the mineralocorticoid receptor (MR). However, our data demonstrate that instead, MBG interferes with the functioning of the MR by inhibiting the transcriptional activity of the receptor, and this is reflected in a reduced interaction between the SRC-3 coactivator and the MR. Thus, the ability of MBG to cause a natriuresis may be due, not only to inhibition of Na+/K+-ATPase activity, but also to its ability to interfere with MR-dependent expression of the Na/K/H exchanger in the late distal nephron.