Flavonoids stimulate Cl conductance of human airway epithelium in vitro and in vivo.

  title={Flavonoids stimulate Cl conductance of human airway epithelium in vitro and in vivo.},
  author={Beate Illek and Horst Fischer},
  journal={American journal of physiology. Lung cellular and molecular physiology},
  volume={275 5},
  • B. Illek, H. Fischer
  • Published 1 November 1998
  • Biology
  • American journal of physiology. Lung cellular and molecular physiology
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… 
Genistein activates CFTR-mediated Cl(-) secretion in the murine trachea and colon.
It is concluded that genistein activates CFTR-mediated Cl(-) secretion in the murine trachea and distal colon and restoration of a human CFTR cDNA-liposome complex to the airways of CF null mice restored the genisteIn response in the tracheas to wild-type levels.
The flavonol quercetin activates basolateral K+ channels in rat distal colon epithelium
It is concluded that at least part of the quercetin‐induced Cl− secretion can be explained by an activation of basolateral K+ channels.
Benzoquinolines and chloride secretion in murine colonic epithelium
  • A. Cuthbert
  • Chemistry, Biology
    British journal of pharmacology
  • 2003
Five compounds related chemically to phenanthrolines, including 5,6‐ and 7,8‐benzoquinoline, may be useful starting points for the synthesis of more potent agents by the addition of ring substituents by the additions of ring nitrogens.
Quercetin stimulates Na+/K+/2Cl- cotransport via PTK-dependent mechanisms in human airway epithelium.
Observations indicate that quercetin stimulates Cl(-) secretion by activating NKCC1 via translocation of anNKCC1-activating factor through an EGFR kinase-dependent pathway.
Cocoa-related flavonoids inhibit CFTR-mediated chloride transport across T84 human colon epithelia.
The data indicate that cocoa flavanols target intestinal CFTR Cl- transport and may serve as mild inhibitors of cAMP-stimulated Cl- secretion in the intestine.
Two mechanisms of genistein inhibition of cystic fibrosis transmembrane conductance regulator Cl− channels expressed in murine cell line
Channel block was relieved by pyrophosphate and ATP, two agents that interact with the nucleotide‐binding domains (NBDs) of CFTR to greatly stimulate channel activity and suggest that the anionic form of genistein may inhibit CFTR.
Activation of Chloride Secretion by Isoflavone Genistein in Endometrial
The soy isoflavone, genistein, stimulates Cl - secretion in endometrial epithelial cells possibly via a direct activation of CFTR which appears to be modulated through a tyrosine kinase-dependent pathway.
Structural determinants for activation and block of CFTR-mediated chloride currents by apigenin.
It is concluded that apigenin binds to a stimulatory and an inhibitory binding site, which are distinguished by their affinities and the molecular interactions during binding.
Effect of genistein on native epithelial tissue from normal individuals and CF patients and on ion channels expressed in Xenopus oocytes
Genistein is able to activate luminal CFTR Cl− conductance in non‐CF tissues and mutant CFTR in oocytes, however, additional inhibitory effects on basolateral K+ conductance and missing effects in native CF tissues do not support the use for pharmacological intervention in CF.
The Chemopreventive Agent Resveratrol Stimulates Cyclic AMP–Dependent Chloride Secretion In vitro
The main mechanism of action of resveratrol in intestinal epithelia is cAMP-induced chloride secretion which can be suppressed by butyrate, suggesting that in cancer chemoprevention, both agents should be combined to reduce an undesired side effect such as diarrhea and to benefit from the known agonistic effect of both agents on differentiation of colon cancer cells.


Alternate stimulation of apical CFTR by genistein in epithelia.
In intact epithelia, the overall secretory response to genistein is composed of stimulatory effects on the apical CFTR and inhibitoryeffects on the basolateral K+ conductance, which is proposed to be a phosphatase, which regulates CFTR during cAMP-dependent stimulation.
Citrus flavonoids stimulate secretion by human colonic T84 cells.
It is shown that dietary citrus flavonoids may modulate colonic secretion, possibly through direct interaction with intracellular secretory pathways, and that tangeritin and nobiletin stimulated Cl- secretion via the cAMP pathway; however, these flavonoid did not stimulate cAMP production to the extent seen with vasoactive intestinal peptide.
CFTR in Calu-3 human airway cells: channel properties and role in cAMP-activated Cl- conductance.
Calu-3, a cell line derived from a lung adenocarcinoma, forms tight junctions, expresses cystic fibrosis transmembrane conductance regulator (CFTR), and secretes Cl- in response to adenosine 3',5'-cyclic monophosphate (cAMP)-elevating agents, which is the predominant pathway for cAMP-stimulated Cl- conductance in Calu- 3 cells.
Vasoactive intestinal peptide, forskolin, and genistein increase apical CFTR trafficking in the rectal gland of the spiny dogfish, Squalus acanthias. Acute regulation of CFTR trafficking in an intact epithelium.
The intact shark rectal gland is used as a model tissue in which salt secretion is dynamically regulated and both chloride secretion and cellular CFTR immunofluorescence can be quantified in parallel to provide the first quantitative morphological evidence for acute hormonal regulation of CFTR trafficking in an intact epithelial tissue.
Tyrosine phosphorylation is a novel pathway for regulation of chloride secretion in shark rectal gland.
Genistein induces bumetanide-sensitive chloride secretion in both perfused rectal glands and cultured tubular cells, indicating that genistein-induced secretion is not mediated by the cAMP-protein kinase A pathway, and genisteIn-sensitive peptides are present in the rectal gland cell and are candidates for involvement in the regulation of chloride secretion.
A volume-sensitive chloride conductance in human colonic cell line T84.
The chloride-secreting colonic cell line, T84, was studied under whole cell patch clamp with Cl as the permeant ion in pipette and bath solutions to suggest that an isosmotic pipette filling solution behaves as if it is hypertonic by approximately 60 mosmol/kgH2O to the bath.
Swelling-induced and depolarization-induced C1-channels in normal and cystic fibrosis epithelial cells.
Cl- currents induced by cell swelling were characterized at the whole cell and single-channel levels in primary cultures of normal and cystic fibrosis (CF) epithelial cells and in the T84 cell line and some consistent differences were observed.
Direct Activation of Cystic Fibrosis Transmembrane Conductance Regulator Channels by 8-Cyclopentyl-1,3-dipropylxanthine (CPX) and 1,3-Diallyl-8-cyclohexylxanthine (DAX)*
It is reported here that the same low concentrations of both CPX and DAX which activate chloride currents from cells also generate a profound activation of CFTR channels incorporated into planar lipid bilayers.
Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study.
The antiaggregatory effects of flavonoids seen in vitro are due to concentrations that cannot be attained in vivo, and effects of dietary flavonols and flavones on cardiovascular risk are possibly not mediated by hemostatic variables.