apigenin and daidzein

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.

Topics: Animals; Calcium-Calmodulin-Dependent Protein Kinases; Carrier Proteins; Cell Line; Cell Membrane; Chamomile; Chloride Channels; Electrophysiology; Enzyme Inhibitors; Epithelial Cells; Flavonoids; Genistein; Isoflavones; Kidney; Membrane Potentials; Oils, Volatile; Plants, Medicinal; Protein-Tyrosine Kinases; Sodium-Potassium-Chloride Symporters; Structure-Activity Relationship

Flavonoid and isoflavonoid glycosides are common dietary phenolics which may be absorbed from the small intestine of humans. The ability of cell-free extracts from human small intestine and liver to deglycosylate various (iso)flavonoid glycosides was investigated. Quercetin 4'-glucoside, naringenin 7-glucoside, apigenin 7-glucoside, genistein 7-glucoside and daidzein 7-glucoside were rapidly deglycosylated by both tissue extracts, whereas quercetin 3,4'-diglucoside, quercetin 3-glucoside, kaempferol 3-glucoside, quercetin 3-rhamnoglucoside and naringenin 7-rhamnoglucoside remained unchanged. The Km for hydrolysis of quercetin 4'-glucoside and genistein 7-glucoside was approximately 32+/-12 and approximately 14+/-3 microM in both tissues respectively. The enzymatic activity of the cell-free extracts exhibits similar properties to the cytosolic broad-specificity -glucosidase previously described in mammals.

Topics: beta-Glucosidase; Cell Extracts; Cell-Free System; Chamomile; Cytosol; Flavanones; Flavonoids; Genistein; Gluconates; Glycosides; Glycosylation; Humans; Inositol; Intestine, Small; Isoflavones; Lactones; Liver; Oils, Volatile; Plants, Medicinal; Quercetin; Rutin; Taurocholic Acid