Effect of genistein on native epithelial tissue from normal individuals and CF patients and on ion channels expressed in Xenopus oocytes.

Details

Serval ID
serval:BIB_3B8D369C5954
Type
Article: article from journal or magazin.
Collection
Publications
Title
Effect of genistein on native epithelial tissue from normal individuals and CF patients and on ion channels expressed in Xenopus oocytes.
Journal
British Journal of Pharmacology
Author(s)
Mall M., Wissner A., Seydewitz H.H., Hübner M., Kuehr J., Brandis M., Greger R., Kunzelmann K.
ISSN
0007-1188 (Print)
ISSN-L
0007-1188
Publication state
Published
Issued date
2000
Peer-reviewed
Oui
Volume
130
Number
8
Pages
1884-1892
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
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.
Keywords
1-Methyl-3-isobutylxanthine/pharmacology, Adolescent, Adult, Aged, Amiloride/pharmacology, Animals, Child, Child, Preschool, Cystic Fibrosis/physiopathology, Cystic Fibrosis Transmembrane Conductance Regulator/drug effects, Cystic Fibrosis Transmembrane Conductance Regulator/genetics, Dose-Response Relationship, Drug, Epithelium/drug effects, Epithelium/physiopathology, Female, Forskolin/pharmacology, Gene Expression, Genistein/pharmacology, Humans, Ion Channels/drug effects, Ion Channels/genetics, Ion Transport/drug effects, Membrane Potentials/drug effects, Middle Aged, Mutation, Nasal Cavity/drug effects, Nasal Cavity/physiopathology, Oocytes, Rectum/drug effects, Rectum/physiopathology, Sodium Channels/drug effects, Xenopus
Pubmed
Web of science
Open Access
Yes
Create date
05/08/2012 11:24
Last modification date
20/08/2019 13:31
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