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  • Title: Flavonoids stimulate Cl conductance of human airway epithelium in vitro and in vivo.
    Author: Illek B, Fischer H.
    Journal: Am J Physiol; 1998 Nov; 275(5):L902-10. PubMed ID: 9815107.
    Abstract:
    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 microM) </= apigenin (11.2 +/- 2.1 microM) </= genistein (13.6 +/- 3.5 microM) </= quercetin (22.1 +/- 4.5 microM). Stimulation of monolayers with forskolin significantly increased their sensitivity to flavonoids: kaempferol (2.5 +/- 0.7 microM) </= apigenin (3.4 +/- 0.9 microM) </= quercetin (4.1 +/- 0.7 microM) </= genistein (6.9 +/- 2.2 microM). 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.
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