Ca2+ signals evoked by histamine H1 receptors are attenuated by activation of prostaglandin EP2 and EP4 receptors in human aortic smooth muscle cells
Ca2+ signals evoked by histamine H1 receptors are attenuated by activation of prostaglandin EP2 and EP4 receptors in human aortic smooth muscle cells
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DOI：
10.1111/bph.12239
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发表时间：
2013-08-01
影响因子：
7.3
通讯作者：
Taylor, Colin W.
中科院分区：
文献类型：
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作者：
Pantazaka, Evangelia;Taylor, Emily J. A.;Taylor, Colin W.
背景和目的组胺和前列腺素E-2(PGE(2))直接或通过对其他细胞的作用调节血管平滑肌(VSM)的行为，但它们对人VSM的作用尚未完全消除。实验方法：观察PGE(2)对培养的人主动脉平滑肌细胞(ASMC)内组胺诱导的细胞内游离钙离子浓度([Ca~(2+)](I))和腺苷环化酶活性的影响。组胺和EP受体的选择性配基被用来识别介导反应的受体。KEY结果组胺通过H-1受体刺激[Ca~(2+)](I)增加，这完全是通过激活肌醇1，4，5-三磷酸受体来实现的。选择性刺激EP2或EP4受体可减弱组胺诱导的钙信号，但PGE(2)对钙信号和AC活性的影响在很大程度上是由EP2受体介导的。结论和意义两种重要的炎症介质，组胺通过H-1受体和PGE(2)主要通过EP2受体作用，对人ASMCs的[Ca~(2+)](I)起相反的作用。
BACKGROUND AND PURPOSEHistamine and prostaglandin E-2 (PGE(2)), directly and via their effects on other cells, regulate the behaviour of vascular smooth muscle (VSM), but their effects on human VSM are incompletely resolved.EXPERIMENTAL APPROACHThe effects of PGE(2) on histamine-evoked changes in intracellular free Ca2+ concentration ([Ca2+](i)) and adenylyl cyclase activity were measured in populations of cultured human aortic smooth muscle cells (ASMCs). Selective ligands of histamine and EP receptors were used to identify the receptors that mediate the responses.KEY RESULTSHistamine, via H-1 receptors, stimulates an increase in [Ca2+](i) that is entirely mediated by activation of inositol 1,4,5-trisphosphate receptors. Selective stimulation of EP2 or EP4 receptors attenuates histamine-evoked Ca2+ signals, but the effects of PGE(2) on both Ca2+ signals and AC activity are largely mediated by EP2 receptors. CONCLUSIONS AND IMPLICATIONS Two important inflammatory mediators, histamine via H-1 receptors and PGE(2) acting largely via EP2 receptors, exert opposing effects on [Ca2+](i) in human ASMCs.