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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Nuclear membrane receptors and channels as targets for drug development in cardiovascular diseases.
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Nuclear membrane receptors and channels as targets for drug development in cardiovascular diseases.

机译:核膜受体和通道是心血管疾病药物开发的目标。

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The use of confocal microscopy has shown that the nucleus plays an important role in excitation-contraction and excitation-secretion coupling of several excitable and nonexcitable cardiovascular cells. It has shown that the nuclear membranes, like the sarcolemmal membrane, possess ionic transporters as well as G protein-coupled receptors (GPCRs), which play a major role in modulating both cytosolic and nuclear ionic homeostasis and nuclear signalling. During spontaneous contraction of heart cells, the increase in cytosolic Ca2+ was immediately followed by a transient increase in nuclear Ca2+. The nuclear Ca2+ rise during excitation-contraction and excitation-secretion coupling was both dependent and independent of changes in cytosolic Ca2+. Nuclear membrane GPCRs, such as those of angiotensin II, neuropeptide Y, and ET-1, were functional and contributed to modulation of nuclear ionic homeostasis via direct and (or) indirect modulation of nuclear membrane ionic transporters such as channels, pumps, and exchangers. The signalling of nuclear membrane GPCRs may also contribute to modulation of gene expression, which may regulate proliferation and remodelling of cells and, indeed, life and death. Direct or indirect targeting of nuclear membrane ionic transporters and GPCRs may constitute a new target for drug action.
机译:共聚焦显微镜的使用表明,核在几种可兴奋和不可兴奋的心血管细胞的兴奋收缩和兴奋分泌结合中起着重要作用。研究表明,核膜像肌膜一样,具有离子转运蛋白和G蛋白偶联受体(GPCR),它们在调节细胞溶质和核离子稳态和核信号传导中均起着重要作用。在心脏细胞自发收缩期间,胞质Ca2 +的增加立即被核Ca2 +的瞬时增加所跟随。在激发-收缩和激发-分泌偶联过程中,核Ca2 +的上升既依赖于胞质Ca2 +的变化,又与之无关。诸如血管紧张素II,神经肽Y和ET-1的核膜GPCR具有功能,并通过直接和(或)间接调节核膜离子转运蛋白(如通道,泵和交换器)来调节核离子稳态。 。核膜GPCR的信号转导也可能有助于基因表达的调节,从而调节细胞的增殖和重塑,甚至调节生与死。直接或间接靶向核膜离子转运蛋白和GPCR可能构成药物作用的新靶标。

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