Nongenomic effect of aldosterone on Na+,K+-adenosine triphosphatase in arterial vessels
Nongenomic effect of aldosterone on Na+,K+-adenosine triphosphatase in arterial vessels
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DOI：
10.1210/en.2002-220950
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发表时间：
2003-04-01
期刊：
影响因子：
4.8
通讯作者：
Michea, L
中科院分区：
文献类型：
--
作者：
Alzamora, R;Marusic, ET;Michea, L
在慢性条件下，醛固酮可增加多种组织的Na+，K+-三磷酸腺苷酶(Na+，K+-ATPase)泵的活性和丰度，包括大鼠动脉血管。本研究旨在探讨醛固酮对大鼠主动脉Na+，K+-ATPase是否也有短期影响。泵功能测定为哇巴因敏感的Rb-86/K在主动脉环的摄取。加入醛固酮后，Na+，K+-ATPase迅速受到抑制(为对照组的57.0+/-2.3%；P<；0.05；n=8)，然后在120分钟后恢复到对照组水平。新的盐皮质激素受体拮抗剂依普利酮可阻止醛固酮诱导的哇巴因敏感的RB-86/K摄取减少。抑制基因转录(放线菌素D)或蛋白质合成(放线菌素)对醛固酮对Na+，K+-ATPase的短期作用无影响。在钠离子载体莫能菌素的存在下，也观察到了快速的醛固酮抑制作用。雷帕霉素，一种稳定热休克蛋白-类固醇受体复合体的免疫抑制药物，阻断了快速的醛固酮效应。蛋白激酶C的抑制剂双吲哚I也阻断了醛固酮对钠泵的非基因组作用。微管破碎剂(秋水仙碱)可抑制醛固酮的非基因组效应。质膜蛋白生物素化和Western印迹显示细胞表面Na+，K+-ATPase催化亚型的存在减少。我们的发现表明，醛固酮对血管组织的Na+，K+-ATPase具有非基因组效应。这种作用是通过蛋白激酶C的激活来实现的，这意味着细胞表面催化亚基的丰度降低。这些观察结果与我们之前关于慢性激素替代的报告一起表明，醛固酮通过钠泵调节直接参与血管系统的离子细胞内稳态。
Aldosterone increases Na+,K+-adenosine triphophatase (Na+,K+-ATPase) pump activity and abundance under chronic conditions in several tissues, including rat arterial vessels. The present study was undertaken to evaluate whether aldosterone has also short-term effects on the Na+,K+-ATPase of rat aorta. The pump function was measured as ouabain-sensitive Rb-86/K uptake in aortic rings. Addition of aldosterone induced a rapid inhibition of the Na+,K+-ATPase (57.0 +/- 2.3% of control values; P < 0.05; n = 8), followed by a return to control values after 120 min. The aldosterone-induced decrease in ouabain-sensitive Rb-86/K uptake was prevented by the new mineralocorticoid receptor antagonist eplerenone. The inhibition of gene transcription (actinomycin D) or protein synthesis (cycloheximide) had no effect on short-term aldosterone action on Na+,K+-ATPase. The rapid aldosterone inhibition was also observed in the presence of monensin, a sodium-specific ionophore. Rapamycin, an immunosuppressive drug that stabilizes the heat shock protein-steroid receptor complex, blocked the rapid aldosterone effect. Bisindole I, an inhibitor of protein kinase C, also blocked nongenomic action of aldosterone on the Na pump. The nongenomic effect of aldosterone was inhibited by disrupters of microtubule (colchicine). Plasma membrane protein biotinylation of aortic segments and Western blot indicated a diminished presence of catalytic isoforms of Na+,K+-ATPase on the cell surface. Our findings indicate that aldosterone has a nongenomic effect on the Na+,K+-ATPase of vascular tissue. This effect is mediated through protein kinase C activation and implies reduced cell surface abundance of catalytic subunits. These observations together with our previous report on chronic hormone replacement suggest that aldosterone is directly involved in ionic cellular homeostasis of the vascular system through Na pump regulation.