Activation of Cl- channel and Na+/K+/2Cl- cotransporter in renal epithelial A6 cells by flavonoids: genistein, daidzein, and apigenin.

The present study investigates regulation of Cl- channels and Na+/K+/2Cl- cotransporter in a renal epithelial cell line, A6, by flavones: genistein [an inhibitor of protein tyrosine kinases (PTK)], daidzein (an inactive compound of genistein), and apigenin [an inhibitor of mitogen-activated protein (MAP) kinase]. Genistein and daidzein activated Cl- channels. Genistein and apigenin had a stimulatory effect on the bumetanide-sensitive Na+/K+/2Cl- cotransporter. Other PTK inhibitors, tyrphostin A23, lavendustin A, and herbimycin A, which do not contain a structure flavone, had no stimulatory action on Cl- channels or the Na+/K+/2Cl- cotransporter. These observations conclude that (i) genistein activates a Cl- channel and the Na+/K+/2Cl- cotransporter; and (ii) the stimulatory action is not mediated through its inhibitory action on protein tyrosine kinase, but rather the structure of flavone itself plays a crucial role in stimulatory regulation of Cl- channels and Na+/K+/2Cl- cotransporter. Copyright 1999 Academic Press.