Contrasting effects of cPLA 2 on epithelial Na + transport

• Published in: American Journal of Physiology: Cell Physiology 2001-07, Vol.281 (1), p.C147-C156
• Main Authors: Worrell, Roger T., Bao, Hui-Fang, Denson, Don D., Eaton, Douglas C.
• Format: Article
• Language: English
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.2001.281.1.C147

Activity of the epithelial Na + channel (ENaC) is the limiting step for discretionary Na + reabsorption in the cortical collecting duct. Xenopus laeviskidney A6 cells were used to investigate the effects of cytosolic phospholipase A 2 (cPLA 2 ) activity on Na + transport. Application of aristolochic acid, a cPLA 2 inhibitor, to the apical membrane of monolayers produced a decrease in apical [ 3 H]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 cPLA 2 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 E 2 (PGE 2 ). This suggests that cPLA 2 activity and free AA, which is metabolized to PGE 2 , 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.