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Modulation of Calcium Movements by Urocortin II in Endothelial Cells

机译:Urocortin II在内皮细胞中对钙运动的调节

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Background: In endothelial cells urocortin II has recently been found to activate nitric oxide synthase through cAMP-dependent and Ca2+-related pathway. Aim: The present study was therefore planned to determine the mechanisms of urocortin II effect on Ca2+ movements. Methods. In Fura-2 loaded porcine aortic endothelial cells (PAE), the effects of urocortin II on [Ca2+]c were analyzed and compared with those of various K+ channels agonists/antagonists. Results: In Fura-2 loaded PAE, urocortin II promoted a transient increase of [Ca2+]c mainly originating from an intracellular pool sensitive to thapsigargin and slightly from the extracellular space. In addition, urocortin II caused the hyperpolarization of plasma membrane through the opening of K+ channels, which contributed to the increased [Ca2+]c. These effects were abolished by the corticotropin releasing factor receptors (CRFR2) blocker, the adenylyl cyclase and Ca2+-calmodulin-kinase (CaMKII) inhibitors and by blockers of K+ channels. In addition, in PAE cultured in Na+-free medium or loaded with the plasma-membrane Ca2+ pump inhibitor the urocortin II-evoked Ca2+ transient was slower. Conclusion: The results obtained show that urocortin II affects intracellular Ca2+ homeostasis in PAE by both promoting a discharge of intracellular pool and by interfering with the operation of store-dependent channels through CRFR2-cAMP-CaMKII related signalling and K+ channels opening.
机译:背景:最近发现在内皮细胞中,尿皮质素II通过cAMP依赖性和Ca2 +相关途径激活一氧化氮合酶。目的:因此,本研究计划确定尿皮质素II对Ca2 +运动的作用机制。方法。在装有Fura-2的猪主动脉内皮细胞(PAE)中,分析了尿皮质素II对[Ca2 +] c的作用,并将其与各种K +通道激动剂/拮抗剂的作用进行了比较。结果:在Fura-2负载的PAE中,urocortin II促进了[Ca2 +] c的瞬时增加,其主要来自对毒胡萝卜素敏感的细胞内池,略微来自细胞外空间。此外,urocortin II通过打开K +通道引起质膜超极化,从而导致[Ca2 +] c升高。这些作用被促肾上腺皮质激素释放因子受体(CRFR2)阻滞剂,腺苷酸环化酶和Ca2 +-钙调蛋白激酶(CaMKII)抑制剂以及K +通道阻滞剂消除。此外,在无Na +培养基中培养或加载有血浆膜Ca2 +泵抑制剂的PAE中,urocortin II诱发的Ca2 +瞬变较慢。结论:获得的结果表明,尿皮质素II通过促进细胞内池的放电以及通过CRFR2-cAMP-CaMKII相关信号传导和K +通道开放干扰存储依赖通道的运行,从而影响PAE中的细胞内Ca2 +稳态。

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