Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Br J Pharmacol
2000 Aug 01;1308:1884-92. doi: 10.1038/sj.bjp.0703520.
Show Gene links
Show Anatomy links
Effect of genistein on native epithelial tissue from normal individuals and CF patients and on ion channels expressed in Xenopus oocytes.
Mall M
,
Wissner A
,
Seydewitz HH
,
Hübner M
,
Kuehr J
,
Brandis M
,
Greger R
,
Kunzelmann K
.
???displayArticle.abstract???
The flavonoid genistein has been shown to activate a Cl(-) conductance in various cell types expressing CFTR. We examined if similar effects can be observed when genistein is applied to native ex vivo tissues from human respiratory tract and rectum. We further compared the effects when genistein was applied to oocytes of Xenopus laevis expressing CFTR. In oocytes, both wtCFTR and DeltaF508-CFTR were activated by genistein while both cyclic AMP (K(v)LQT1) and Ca(2+) (SK4) activated K(+) channels were inhibited at high concentrations of genistein. Biopsies from nasal polyps and rectal mucosa were obtained from normal individuals (non-CF) and CF patients and in the presence of amiloride (10 micromol l(-1); mucosal side) the effects of genistein were assessed using a perfused Ussing chamber. In non-CF airway epithelia, genistein (50 micromol l(-1); mucosal side) increased lumen negative I(sc) but had no additional effects on tissues pre-stimulated with IBMX and forskolin (100 micromol l(-1) and 1 micromol l(-1); both sides). In non-CF rectal biopsies, in the presence of amiloride (10 micromol l(-1); mucosal side) and indomethacin (10 micromol l(-1); basolateral side), genistein increased lumen negative I(sc) and enabled cholinergic (carbachol; CCH, 100 micromol l(-1); basolateral side) stimulation of Cl(-) secretion indicating activation of luminal CFTR Cl(-) channels. However, after stimulation with IBMX/forskolin, genistein induced opposite effects and significantly inhibited CCH activated I(sc). In CF airway and intestinal tissues genistein failed to induce Cl(-) secretion. Thus, 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.
Becq,
Development of substituted Benzo[c]quinolizinium compounds as novel activators of the cystic fibrosis chloride channel.
1999, Pubmed
Becq,
Development of substituted Benzo[c]quinolizinium compounds as novel activators of the cystic fibrosis chloride channel.
1999,
Pubmed
Bischof,
Role for tyrosine kinases in carbachol-regulated Ca entry into colonic epithelial cells.
1995,
Pubmed
Boucher,
Evidence for reduced Cl- and increased Na+ permeability in cystic fibrosis human primary cell cultures.
1988,
Pubmed
Cermak,
Dietary flavonol quercetin induces chloride secretion in rat colon.
1998,
Pubmed
Chiang,
Genistein directly induces cardiac CFTR chloride current by a tyrosine kinase-independent and protein kinase A-independent pathway in guinea pig ventricular myocytes.
1997,
Pubmed
Diener,
Modulation of Cl- secretion in rat distal colon by genistein, a protein tyrosine kinase inhibitor.
1996,
Pubmed
French,
Genistein activates CFTR Cl- channels via a tyrosine kinase- and protein phosphatase-independent mechanism.
1997,
Pubmed
Hardcastle,
Failure of cholinergic stimulation to induce a secretory response from the rectal mucosa in cystic fibrosis.
1991,
Pubmed
Hipper,
Mutations in the putative pore-forming domain of CFTR do not change anion selectivity of the cAMP activated Cl- conductance.
1995,
Pubmed
,
Xenbase
Hwang,
Genistein potentiates wild-type and delta F508-CFTR channel activity.
1997,
Pubmed
Illek,
Flavonoids stimulate Cl conductance of human airway epithelium in vitro and in vivo.
1998,
Pubmed
Illek,
cAMP-independent activation of CFTR Cl channels by the tyrosine kinase inhibitor genistein.
1995,
Pubmed
Illek,
Defective function of the cystic fibrosis-causing missense mutation G551D is recovered by genistein.
1999,
Pubmed
Illek,
Alternate stimulation of apical CFTR by genistein in epithelia.
1996,
Pubmed
Joiner,
hSK4, a member of a novel subfamily of calcium-activated potassium channels.
1997,
Pubmed
Kunzelmann,
Defects in processing and trafficking of cystic fibrosis transmembrane conductance regulator.
2000,
Pubmed
Kunzelmann,
The cystic fibrosis transmembrane conductance regulator and its function in epithelial transport.
1999,
Pubmed
Mall,
Cholinergic ion secretion in human colon requires coactivation by cAMP.
1998,
Pubmed
Mall,
CFTR-mediated inhibition of epithelial Na+ conductance in human colon is defective in cystic fibrosis.
1999,
Pubmed
Mall,
cAMP stimulation of CFTR-expressing Xenopus oocytes activates a chromanol-inhibitable K+ conductance.
1996,
Pubmed
,
Xenbase
Mall,
Defective cholinergic Cl(-) secretion and detection of K(+) secretion in rectal biopsies from cystic fibrosis patients.
2000,
Pubmed
Mall,
The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways.
1998,
Pubmed
Murthy,
Coexpression of ligand-gated P2X and G protein-coupled P2Y receptors in smooth muscle. Preferential activation of P2Y receptors coupled to phospholipase C (PLC)-beta1 via Galphaq/11 and to PLC-beta3 via Gbetagammai3.
1998,
Pubmed
Obayashi,
On the mechanism of genistein-induced activation of protein kinase A-dependent Cl- conductance in cardiac myocytes.
1999,
Pubmed
Randak,
Inhibition of ATPase, GTPase and adenylate kinase activities of the second nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator by genistein.
1999,
Pubmed
Reenstra,
CFTR chloride channel activation by genistein: the role of serine/threonine protein phosphatases.
1996,
Pubmed
Rosenstein,
The diagnosis of cystic fibrosis: a consensus statement. Cystic Fibrosis Foundation Consensus Panel.
1998,
Pubmed
Schorderet-Slatkine,
Forskolin increases cAMP and inhibits progesterone induced meiosis reinitiation in Xenopus laevis oocytes.
1982,
Pubmed
,
Xenbase
Schultz,
Pharmacology of CFTR chloride channel activity.
1999,
Pubmed
Sears,
Genistein and tyrphostin 47 stimulate CFTR-mediated Cl- secretion in T84 cell monolayers.
1995,
Pubmed
Shah,
The pharmacology of hSK1 Ca2+-activated K+ channels expressed in mammalian cell lines.
2000,
Pubmed
,
Xenbase
Sheppard,
Structure and function of the CFTR chloride channel.
1999,
Pubmed
Shuba,
Synergistic activation of guinea-pig cardiac cystic fibrosis transmembrane conductance regulator by the tyrosine kinase inhibitor genistein and cAMP.
1997,
Pubmed
Tsui,
Genotype and phenotype in cystic fibrosis.
1997,
Pubmed
Veeze,
Ion transport abnormalities in rectal suction biopsies from children with cystic fibrosis.
1991,
Pubmed
Warth,
Molecular and functional characterization of the small Ca(2+)-regulated K+ channel (rSK4) of colonic crypts.
1999,
Pubmed
,
Xenbase
Warth,
The cAMP-regulated and 293B-inhibited K+ conductance of rat colonic crypt base cells.
1996,
Pubmed
Weinreich,
Direct action of genistein on CFTR.
1997,
Pubmed
,
Xenbase
