GPER regulates endothelin-dependent vascular tone and intracellular calcium.
GPER regulates endothelin-dependent vascular tone and intracellular calcium.
复制标题
DOI：
10.1016/j.lfs.2012.01.007
复制
发表时间：
2012-10-15
期刊：
影响因子：
6.1
通讯作者：
Prossnitz, Eric R.
中科院分区：
文献类型：
--
作者：
Meyer, Matthias R.;Field, Angela S.;Kanagy, Nancy L.;Barton, Matthias;Prossnitz, Eric R.
血管平滑肌细胞内钙离子浓度（VSMC [Ca ~（2+）]i）的增加是内皮素-1（ET-1）诱导的血管收缩的必要条件。基于以前的研究结果，即G蛋白偶联雌激素受体（GPER）的激活抑制血管收缩反应ET-1和调节[Ca ~（2+）]i在培养的VSMC，我们调查是否内源性GPER调节ET-1诱导的VSMC [Ca ~（2+）]i的变化和完整的动脉收缩。将GPER缺陷型（GPER 0）和野生型（WT）小鼠的加压颈动脉用钙指示剂fura 2-AM加载。用GPER选择性激动剂G-1或溶剂刺激动脉，然后暴露于ET-1。同时记录动脉内径和VSMC [Ca 2 +]i的变化。通过qPCR测定ETA和ETB受体的血管基因表达水平。与WT小鼠的动脉相比，GPER 0的动脉中ET-1依赖性血管收缩增加。尽管GPER对ET-1的收缩作用更强，但GPER缺乏与ET-1刺激的VSMC [Ca ~（2+）]i增加显著减少相关，表明肌丝对[Ca ~（2+）]i的力敏感性增加。G-1激活GPER对血管收缩和VSMC对ET-1的[Ca ~（2+）]i反应无影响，而GPER缺乏不影响ETA或ETB受体的表达水平。这些结果表明，内源性GPER抑制ET-1诱导的血管收缩，这种作用可能与VSMC Ca 2+敏感性降低有关。这代表了GPER可能有助于内源性雌激素在心血管系统中的保护作用的潜在机制。
An increase in intracellular vascular smooth muscle cell calcium concentration (VSMC [Ca2+]i) is essential for endothelin-1 (ET-1)-induced vasoconstriction. Based on previous findings that activation of the G protein-coupled estrogen receptor (GPER) inhibits vasoconstriction in response to ET-1 and regulates [Ca2+]i in cultured VSMC, we investigated whether endogenous GPER regulates ET-1-induced changes in VSMC [Ca2+]i and constriction of intact arteries. Pressurized carotid arteries of GPER-deficient (GPER0) and wildtype (WT) mice were loaded with the calcium indicator fura 2-AM. Arteries were stimulated with the GPER-selective agonist G-1 or solvent followed by exposure to ET-1. Changes in arterial diameter and VSMC [Ca2+]i were recorded simultaneously. Vascular gene expression levels of ETA and ETB receptors were determined by qPCR. ET-1-dependent vasoconstriction was increased in arteries from GPER0 compared to arteries from WT mice. Despite the more potent vasoconstriction to ET-1, GPER deficiency was associated with a marked reduction in the ET-1-stimulated VSMC [Ca2+]i increase, suggesting an increase in myofilament force sensitivity to [Ca2+]i. Activation of GPER by G-1 had no effect on vasoconstriction or VSMC [Ca2+]i responses to ET-1, and expression levels of ETA or ETB receptor were unaffected by GPER deficiency. These results demonstrate that endogenous GPER inhibits ET-1-induced vasoconstriction, an effect that may be associated with reduced VSMC Ca2+ sensitivity. This represents a potential mechanism through which GPER could contribute to protective effects of endogenous estrogen in the cardiovascular system.
登录
查看更多内容
G蛋白偶联的雌激素受体GPER在健康和疾病中。
DOI：
10.1038/nrendo.2011.122
发表时间：
2011-08-16
期刊：
Nature reviews. Endocrinology
影响因子：
--
作者：
通讯作者：
--
G蛋白偶联的雌激素受体GPER/GPR30作为心血管功能的调节剂。
影响因子：
4
作者：
Meyer, Matthias R.;Prossnitz, Eric R.;Barton, Matthias
通讯作者：
Barton, Matthias
DOI：
10.1152/ajpheart.1996.271.3.h1117
发表时间：
1996-09-01
影响因子：
4.8
作者：
Lamping, KG;Nuno, DW
通讯作者：
Nuno, DW
影响因子：
8.3
作者：
Tsang, SY;Yao, XQ;Huang, Y
通讯作者：
Huang, Y
影响因子：
8.3
作者：
Chrissobolis, S;Budzyn, K;Sobey, CG
通讯作者：
Sobey, CG