Quercetin and NPPB‐induced diminution of aldosterone action on Na+ absorption and ENaC expression in renal epithelium

Abstract

In renal epithelial A6 cells, aldosterone applied for 24 h increased the transpithelial Cl− secretion due to activation of the Na+/K+/2Cl− cotransporter (NKCC), 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 NKCC) or NPPB (a blocker of Cl− channel), while 24 h-pretreatment with bumetanide (a blocker of NKCC) 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 effects 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 NKCC, and that modification of activity of Cl− transporter/channel participating in the transepithelial Cl− secretion influences the aldosterone-stimulated ENaC (transepithelial Na+ transport). Supported by Grants-in-Aid from JSPS (17390057, 17590191).