| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Research Institute, Children's Hospital Oakland, Oakland California 94609
The ability of the flavonoids genistein,
apigenin, kaempferol, and quercetin to activate cystic fibrosis
transmembrane conductance regulator-mediated Cl currents in human
airway epithelium was investigated. We used the patch-clamp technique
on single Calu-3 cells, transepithelial measurements in Calu-3
monolayers, and in vivo measurements of nasal potential difference. All
flavonoids stimulated Cl currents in transepithelial experiments dose
dependently. Half-maximal stimulatory concentrations were kaempferol
(5.5 ± 1.7 µM) 
apigenin (11.2 ± 2.1 µM) genistein (13.6 ± 3.5 µM) quercetin (22.1 ± 4.5 µM).
Stimulation of monolayers with forskolin significantly increased their
sensitivity to flavonoids: kaempferol (2.5 ± 0.7 µM) apigenin
(3.4 ± 0.9 µM) quercetin (4.1 ± 0.7 µM) genistein
(6.9 ± 2.2 µM). Forskolin pretreatment significantly reduced the
Hill coefficient
(nH) for all
flavonoids. Control monolayers showed
nH = 2.00 ± 0.21 (all flavonoids combined), and forskolin-stimulated monolayers
showed nH = 1.07 ± 0.07, which was not different among the flavonoids. These data
imply that the activation kinetics and the binding site(s) for
flavonoids were significantly altered by forskolin stimulation. In
whole cell patch-clamp experiments, maximal flavonoid-stimulated
currents (percentage of forskolin-stimulated currents) were apigenin
(429 ± 86%) 
kaempferol (318 ± 45%) genistein (258 ± 20%) = quercetin (256 ± 26%). Stimulation of the currents was
caused by an increase in channel open probability. No other Cl
conductances contributed significantly to the flavonoid-activated Cl
currents in Calu-3 cells. In vivo, flavonoids significantly stimulated
nasal potential difference by, on average, 27.8% of isoproterenol
responses.
chloride conductance; genistein; apigenin; kaempferol; quercetin; cystic fibrosis; cystic fibrosis transmembrane conductance regulator
This article has been cited by other articles:
|
|
 |
|
  H. Fischer, B. Illek, W. E. Finkbeiner, and J. H. Widdicombe Basolateral Cl channels in primary airway epithelial cultures Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1432 - L1443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schuier, H. Sies, B. Illek, and H. Fischer Cocoa-Related Flavonoids Inhibit CFTR-Mediated Chloride Transport across T84 Human Colon Epithelia J. Nutr., October 1, 2005; 135(10): 2320 - 2325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Baker and K. L. Hamilton Genistein stimulates electrogenic Cl- secretion in mouse jejunum Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1636 - C1645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Tong, B. Illek, V. J. Bhagwandin, G. M. Verghese, and G. H. Caughey Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line Am J Physiol Lung Cell Mol Physiol, November 1, 2004; 287(5): L928 - L935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Irokawa, M. E. Krouse, N. S. Joo, J. V. Wu, and J. J. Wine A "virtual gland" method for quantifying epithelial fluid secretion Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L784 - L793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Caci, C. Folli, O. Zegarra-Moran, T. Ma, M. F. Springsteel, R. E. Sammelson, M. H. Nantz, M. J. Kurth, A. S. Verkman, and L. J. V. Galietta CFTR activation in human bronchial epithelial cells by novel benzoflavone and benzimidazolone compounds Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L180 - L188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. C. Sun, C.-B. Zhai, M. Cui, Y. Chen, L. R. Levin, J. Buck, and J. A. Bonanno HCO-3-dependent soluble adenylyl cyclase activates cystic fibrosis transmembrane conductance regulator in corneal endothelium Am J Physiol Cell Physiol, May 1, 2003; 284(5): C1114 - C1122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kunzelmann and M. Mall Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease Physiol Rev, January 1, 2002; 82(1): 245 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. J. Galietta, S. Jayaraman, and A. S. Verkman Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists Am J Physiol Cell Physiol, November 1, 2001; 281(5): C1734 - C1742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Fischer, N. Fukuda, P. Barbry, B. Illek, C. Sartori, and M. A. Matthay Partial restoration of defective chloride conductance in {Delta}F508 CF mice by trimethylamine oxide Am J Physiol Lung Cell Mol Physiol, July 1, 2001; 281(1): L52 - L57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Illek, M. E. Lizarzaburu, V. Lee, M. H. Nantz, M. J. Kurth, and H. Fischer Structural determinants for activation and block of CFTR-mediated chloride currents by apigenin Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1838 - C1846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Singh, B. D. Schultz, J. A. Katzenellenbogen, E. M. Price, R. J. Bridges, and N. A. Bradbury Estrogen Inhibition of Cystic Fibrosis Transmembrane Conductance Regulator-Mediated Chloride Secretion J. Pharmacol. Exp. Ther., October 1, 2000; 295(1): 195 - 204. [Abstract] [Full Text]
|
|
|
|
|
|
C. A. Goddard, M. J. Evans, and W. H. Colledge Genistein activates CFTR-mediated Cl- secretion in the murine trachea and colon Am J Physiol Cell Physiol, August 1, 2000; 279(2): C383 - C392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Devor, R. J. Bridges, and J. M. Pilewski Pharmacological modulation of ion transport across wild-type and Delta F508 CFTR-expressing human bronchial epithelia Am J Physiol Cell Physiol, August 1, 2000; 279(2): C461 - C479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Illek, L. Zhang, N. C. Lewis, R. B. Moss, J.-Y. Dong, and H. Fischer Defective function of the cystic fibrosis-causing missense mutation G551D is recovered by genistein Am J Physiol Cell Physiol, October 1, 1999; 277(4): C833 - C839. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Illek, H. Fischer, and T. E. Machen II. Regulation of CFTR by small molecules including HCO-3 Am J Physiol Gastrointest Liver Physiol, December 1, 1998; 275(6): G1221 - G1226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. V. Galietta, M. F. Springsteel, M. Eda, E. J. Niedzinski, K. By, M. J. Haddadin, M. J. Kurth, M. H. Nantz, and A. S. Verkman Novel CFTR Chloride Channel Activators Identified by Screening of Combinatorial Libraries Based on Flavone and Benzoquinolizinium Lead Compounds J. Biol. Chem., June 1, 2001; 276(23): 19723 - 19728. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Fischer, J. H. Widdicombe, and B. Illek Acid secretion and proton conductance in human airway epithelium Am J Physiol Cell Physiol, April 1, 2002; 282(4): C736 - C743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. C. Sun and J. A. Bonanno Expression, localization, and functional evaluation of CFTR in bovine corneal endothelial cells Am J Physiol Cell Physiol, April 1, 2002; 282(4): C673 - C683. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
