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Bisphenol A inhibits Cl(-) secretion by inhibition of basolateral K+ conductance in human airway epithelial cells.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 2002 Jul; Vol. 302 (1), pp. 80-7. - Publication Year :
- 2002
-
Abstract
- There has been growing concern about the potential threat of hormone-disrupting chemicals like bisphenol A to various aspects of animal and human health. We studied the effects of bisphenol A on the Cl(-) secretion in human airway epithelial Calu-3 cells. Pretreatment with bisphenol A (IC(50) = 60 microM, for 30 min) prevented isoproterenol (10 nM)-generated short-circuit current (I(sc)) more potently than 17beta-estradiol or tamoxifen (IC(50) = 1 mM). 5'-Nitro-2-(3-phenylpropylamino) benzoate-sensitive apical conductance potentiated by isoproterenol was not affected by the pretreatment with either of these estrogenic compounds. The effects of bisphenol A were simulated in I(sc) responses to forskolin (10 microM) and 8-bromo-cAMP (1 mM). Nystatin permeabilization of Calu-3 monolayers revealed that bisphenol A attenuated 8-bromo-cAMP-induced basolateral K+ current, which is sensitive to clotrimazole (30 microM) and insensitive to charybdotoxin (100 nM), without affecting the apical Cl(-) current. Bisphenol A, but neither 17beta-estradiol nor tamoxifen, interrupted the charybdotoxin-sensitive component of I(sc) stimulated by 1-ethyl-2-benzimidazolinone (1-EBIO; 500 microM). The inhibitory effects of bisphenol A on these Cl(-) secretory stimuli were remarkable when applied to the apical rather than the basolateral membrane. Alternatively, long-term incubation of bisphenol A (1 microM; 12-72 h) had no discernible effect on isoproterenol- and 1-EBIO-induced Cl(-) secretion. These findings indicate that short-term exposure to bisphenol A attenuates transepithelial Cl(-) secretion through inhibition of both cAMP- and Ca(2+)-activated K+ channels on the basolateral membrane, interacting from the cytosolic surface in Calu-3 cells.
- Subjects :
- Adrenergic beta-Agonists pharmacology
Benzhydryl Compounds
Benzimidazoles pharmacology
Cell Line
Chloride Channel Agonists
Chloride Channels drug effects
Cyclic AMP physiology
Cystic Fibrosis Transmembrane Conductance Regulator biosynthesis
Down-Regulation drug effects
Electrophysiology
Epithelial Cells drug effects
Humans
Isoproterenol pharmacology
Phenotype
Potassium Channels agonists
Respiratory System cytology
Respiratory System drug effects
Respiratory System metabolism
Chlorides metabolism
Epithelial Cells metabolism
Phenols pharmacology
Potassium Channel Blockers
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 302
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 12065703
- Full Text :
- https://doi.org/10.1124/jpet.302.1.80