Quercetin and NPPB-induced diminution of aldosterone action on Na+ absorption and ENaC expression in renal epithelium
Quercetin and NPPB-induced diminution of aldosterone action on Na+ absorption and ENaC expression in renal epithelium
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DOI：
10.1016/j.bbrc.2005.08.096
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发表时间：
2005-10-21
影响因子：
3.1
通讯作者：
Marunaka, Y
中科院分区：
文献类型：
--
作者：
Fujimoto, S;Niisato, N;Marunaka, Y
在肾上皮A6细胞中，应用醛固酮24 h由于Na+/K+/2Cl（-）共转运蛋白的激活而使跨上皮Cl-分泌增加30倍以上，并刺激跨上皮Na+吸收、上皮Na+通道（ENaC）活性和α-ENaC mRNA表达。用槲皮素预处理24 h可减弱醛固酮对跨上皮Na+吸收、ENaC活性和α-ENaC mRNA表达的刺激作用（Na+/K+/2Cl（-）协同转运蛋白的激活剂，参与Cl-进入胞质空间）或5-硝基2-（3-苯丙氨基）苯甲酸酯（NPPB）（一种参与细胞质空间中Cl-释放的Cl-通道阻滞剂），而用Na+/K+/2Cl（-）协同转运体阻断剂布美他尼预处理24 h，可增强醛固酮对Na+跨上皮吸收的促进作用。另一方面，在基础（醛固酮未刺激）条件下，槲皮素，NPPB或布美他尼对跨上皮Na+吸收，ENaC活性或α-ENaC mRNA表达无影响。这些观察结果表明，尽管醛固酮总体上显示出对ENaC（跨上皮Na+转运）的刺激作用，但醛固酮通过激活Na+/K+/2Cl（-）协同转运蛋白对ENaC（跨上皮Na+转运）具有抑制作用，并且参与跨上皮Cl-分泌的Cl-转运蛋白/通道活性的改变影响醛固酮刺激的ENaC（跨上皮Na+转运）。(c)2005年爱思唯尔公司All rights reserved.
In renal epithelial A6 cells, aldosterone applied for 24 h increased the transepithelial Cl- secretion over 30-fold due to activation of the Na+/K+/2Cl(-) cotransporter and stimulated the transepithelial Na+ absorption, activity of epithelial Na+ channel (ENaC), and alpha-ENaC mRNA expression. The stimulatory action of aldosterone on the transepithelial Na+ absorption, ENaC activity, and alpha-ENaC mRNA expression was diminished by 24 h-pretreatment with quercetin (an activator of Na+/K+/2Cl(-) cotransporter participating in Cl- entry into the cytosolic space) or 5-nitro 2-(3-phenylpropylamino)benzoate (NPPB) (a blocker of Cl- channel participating in Cl- release from the cytosolic space), while 24 h-pretreatment with bumetanide (a blocker of Na+/K+/2Cl(-) cotransporter) enhanced the stimulatory action of aldosterone on transepithelial Na+ absorption. On the other hand, under the basal (aldosterone-unstimulated) condition, quercetin, NPPB or bumetanide had no effect on transepithelial Na+ absorption, activity of ENaC or alpha-ENaC mRNA expression. These observations suggest that although aldosterone shows overall its stimulatory action on ENaC (transepithelial Na+ transport), aldosterone has an inhibitory action on ENaC (transepithelial Na+ transport) via activation of the Na+/K+/2Cl(-) cotransporter, and that modification of activity of Cl- transporter/channel participating in the transepithelial Cl- secretion influences the aldosterone-stimulated ENaC (transepithelial Na+ transport). (c) 2005 Elsevier Inc. All rights reserved.