GPR30 expression is required for the mineralocorticoid receptor-independent rapid vascular effects of aldosterone.
GPR30 expression is required for the mineralocorticoid receptor-independent rapid vascular effects of aldosterone.
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DOI：
10.1161/hypertensionaha.110.161653
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Feldman RD
中科院分区：
文献类型：
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作者：
Gros R;Ding Q;Sklar LA;Prossnitz EE;Arterburn JB;Chorazyczewski J;Feldman RD
越来越多的人认识到，类固醇通过快速的、所谓的非基因组信号通路引起急性血管效应。例如，尽管已证实醛固酮通过盐皮质激素受体依赖和非依赖性途径介导快速血管效应，但这种矿物皮质激素受体非依赖性作用的机制(S)尚未确定。对于雌激素，据报道，它的快速作用至少部分是通过跨膜的G蛋白偶联受体GPR30介导的。以往的研究表明，醛固酮和雌激素对GPR30表达的共同反应结果，即激活血管平滑肌细胞磷脂酰肌醇3-激酶依赖的收缩和细胞外信号调节的激酶激活。目前的研究是为了验证一种假说，即平滑肌对醛固酮的快速反应依赖于GPR30依赖的信号通路的可用性。这些发现不仅调和了文献中关于新鲜分离的和培养的主动脉平滑肌细胞对醛固酮反应的差异，而且还建议了体内调节醛固酮对血管系统作用的替代治疗策略。
It has been increasingly appreciated that steroids elicit acute vascular effects through rapid, so-called nongenomic signaling pathways. Though aldosterone, for example, has been demonstrated to mediate rapid vascular effects via both mineralocorticoid receptor-dependent and -independent pathways, the mechanism(s) of this miner-alocorticoid receptor-independent effect of aldosterone is yet to be determined. For estrogen, its rapid effects have been reported to be, at least in part, mediated via the 7-transmembrane-spanning, G protein-coupled receptor GPR30. Previous studies have demonstrated common response outcomes in response to both aldosterone and estrogen on GPR30 expression, ie, activation of phosphatidylinositol 3-kinase-dependent contraction and extracellular signal-regulated kinase activation in vascular smooth muscle cells. The present studies were undertaken to test the hypothesis that the rapid response to aldosterone in smooth muscle is dependent on the availability of a GPR30-dependent signaling pathway. These findings not only reconcile differences in the literature for aldosterone response in freshly isolated versus cultured aortic smooth muscle cells but also suggest alternative therapeutic strategies for modulating aldosterone actions on the vasculature in vivo.