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.
Niisato
Naomi
N
Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Nishino
Hoyoku
H
Nishio
Kyosuke
K
Marunaka
Yoshinori
Y
D000818:Animals; D047310:Apigenin; D002460:Cell Line; D018118:Chloride Channels; D000242:Cyclic AMP / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D014981:Xenopus
D018118:Chloride Channels; D047309:Flavones; D005419:Flavonoids; D028021:Sodium-Potassium-Chloride Symporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D047310:Apigenin; D000242:Cyclic AMP; C043562:flavone