Cross talk of cAMP and flavone in regulation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl − channel and Na +/K +/2Cl − cotransporter in renal epithelial A6 cells

We have reported that in renal epithelial A6 cells flavones stimulate the transepithelial Cl − secretion by activating the cystic fibrosis transmembrane conductance regulator (CFTR) Cl − channel and/or the Na +/K +/2Cl − cotransporter. On the other hand, it has been established that cAMP activates the CFTR Cl − channel and the Na +/K +/2Cl − cotransporter. However, no information is available on the interaction between cAMP and flavones on stimulation of the CFTR Cl − channel and the Na +/K +/2Cl − cotransporter. To clarify the interaction between cAMP and flavones, we studied the regulatory mechanism of the CFTR Cl − channel and the Na +/K +/2Cl − cotransporter by flavones (apigenin, luteolin, kaempherol, and quercetin) under the basal and cAMP-stimulated conditions in renal epithelial A6 cells. Under the basal (cAMP-unstimulated) condition, these flavones stimulated the Cl − secretion by activating the Na +/K +/2Cl − cotransporter without any significant effects on the CFTR Cl − channel activity. On the other hand, these flavones diminished the activity of the cAMP-stimulated Na +/K +/2Cl − cotransporter without any significant effects on the CFTR Cl − channel activity. Interestingly, the level of the flavone-induced Cl − secretion under the basal condition was identical to that under the cAMP-stimulated condition. Based on these results, it is suggested that although both cAMP and flavones activate the Na +/K +/2Cl − cotransporter, these flavones have more powerful effects than cAMP on the Na +/K +/2Cl − cotransporter.