Contrasting effects of cPLA2 on epithelial Na+ transport.
Contrasting effects of cPLA2 on epithelial Na+ transport.
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DOI：
10.1152/ajpcell.2001.281.1.c147
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发表时间：
2001-07
期刊：
影响因子：
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通讯作者：
R. Worrell;H. Bao;D. Denson;D. Eaton
中科院分区：
文献类型：
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作者：
R. Worrell;H. Bao;D. Denson;D. Eaton
上皮Na+通道（ENaC）的活性是皮质集合管中任意Na+重吸收的限制步骤。以非洲爪蟾肾A6细胞为研究对象，探讨了胞浆磷脂酶A2（cPLA 2）活性对Na+转运的影响。应用马兜铃酸，cPLA 2抑制剂，单层的顶端膜产生减少顶端[3 H]花生四烯酸（AA）的释放，并导致跨上皮Na+电流增加约两倍。增加的电流被取消的nonmetabolized AA类似物5，8，11，14-二十碳四炔酸（ETYA），表明AA，而不是其代谢产物之一，影响电流。在单通道研究中，ETYA导致ENaC开放概率降低。这表明cPLA 2在A6细胞中具有张力活性，并且在顶膜处释放的AA的最终效应是通过对ENaC的作用减少Na+转运。与此相反，马兜铃酸应用于基底侧抑制电流，ETYA的效果并不逆转。基底侧应用环氧化酶抑制剂布洛芬也抑制电流。前列腺素E2（PGE 2）可逆转这两种作用。这表明cPLA 2活性和代谢为PGE 2的游离AA是支持转运所必需的。这项研究支持通过调节游离AA和AA代谢来微调Na+转运和重吸收。
Activity of the epithelial Na+ channel (ENaC) is the limiting step for discretionary Na+ reabsorption in the cortical collecting duct. Xenopus laevis kidney A6 cells were used to investigate the effects of cytosolic phospholipase A2 (cPLA2) activity on Na+ transport. Application of aristolochic acid, a cPLA2 inhibitor, to the apical membrane of monolayers produced a decrease in apical [3H]arachidonic acid (AA) release and led to an approximate twofold increase in transepithelial Na+ current. Increased current was abolished by the nonmetabolized AA analog 5,8,11,14-eicosatetraynoic acid (ETYA), suggesting that AA, rather than one of its metabolic products, affected current. In single channel studies, ETYA produced a decrease in ENaC open probability. This suggests that cPLA2 is tonically active in A6 cells and that the end effect of liberated AA at the apical membrane is to reduce Na+ transport via actions on ENaC. In contrast, aristolochic acid applied basolaterally inhibited current, and the effect was not reversed by ETYA. Basolateral application of the cyclooxygenase inhibitor ibuprofen also inhibited current. Both effects were reversed by prostaglandin E2 (PGE2). This suggests that cPLA2 activity and free AA, which is metabolized to PGE2, are necessary to support transport. This study supports the fine-tuning of Na+ transport and reabsorption through the regulation of free AA and AA metabolism.