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, Hubner, M, Kuehr, J, Brandis, M, Greger, R and Kunzelmann, K (2000) Effect of genistein on native epithelial tissue from normal individuals and CF patients and on ion channels expressed in Xenopus oocytes. British Journal of Pharmacology, 130 2: 1884-1892. doi:10.1038/sj.bjp.0703520


Author Mall, M
Wissner, A
Seydewitz, HH
Hubner, M
Kuehr, J
Brandis, M
Greger, R
Kunzelmann, K
Title Effect of genistein on native epithelial tissue from normal individuals and CF patients and on ion channels expressed in Xenopus oocytes
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
Publication date 2000-01-01
Sub-type Article (original research)
DOI 10.1038/sj.bjp.0703520
Open Access Status Not Open Access
Volume 130
Issue 2
Start page 1884
End page 1892
Total pages 9
Place of publication Houndmills, Basingstoke, UK
Publisher Nature Publishing Group
Language eng
Subject C1
730110 Respiratory system and diseases (incl. asthma)
270104 Membrane Biology
Abstract 1 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. 2 In oocytes, both wtCFTR and Delta F508-CFTR were activated by genistein while both cyclic AMP (K(v)LQT1) and Ca2+ (SK4) activated K+ channels were inhibited at high concentrations of genistein. 3 Biopsies from nasal polyps and rectal mucosa were obtained from normal individuals (non-CF) and CF patients and in the presence of amiloride (10 mu mol l(-1); mucosal side) the effects of genistein were assessed using a perfused Ussing chamber. In non-CF airway epithelia, genistein (50 mu mol l(-1); mucosal side) increased lumen negative I-sc but had no additional effects on tissues pre-stimulated with IBMX and forskolin (100 mu mol l(-1) and 1 mu mol l(-1); both sides). 4 In non-CF rectal biopsies, in the presence of amiloride (10 mu mol l(-1); mucosal side) and indomethacin (10 mu mol l(-1); basolateral side), genistein increased lumen negative I-sc and enabled cholinergic (carbachol; CCH, 100 mu mol l(-1); basolateral side) stimulation of Cl- secretion indicating activation of luminal CFTR C-l(-) 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. 5 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.
Keyword Pharmacology & Pharmacy
Cftr
Cystic Fibrosis
Genistein
Flavonoids
Cl- Secretion
Epithelial Transport
Rectal Mucosa
Airways
Transmembrane Conductance Regulator
Tyrosine Kinase Inhibitor
Cystic-fibrosis
Na+ Conductance
Cl Conductance
K+ Conductance
Camp
Activation
Stimulation
Myocytes
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Tue, 10 Jun 2008, 21:33:23 EST