Bisphenol A inhibits Cl(-) secretion by inhibition of basolateral K+ conductance in human airway epithelial cells.
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.
Ito
Yasushi
Y
Division II (Respiratory Division), Internal Medicine II, University of Nagoya School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Sato
Shinji
S
Son
Masami
M
Kondo
Masashi
M
Kume
Hiroaki
H
Takagi
Kenzo
K
Yamaki
Kenichi
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D001559:Benzhydryl Compounds; D001562:Benzimidazoles / Q000494:pharmacology; D002460:Cell Line; D065101:Chloride Channel Agonists; D018118:Chloride Channels / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D004594:Electrophysiology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D010641:Phenotype; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists; D012137:Respiratory System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000098826:Bisphenol A Compounds
D000318:Adrenergic beta-Agonists; D001559:Benzhydryl Compounds; D001562:Benzimidazoles; D065101:Chloride Channel Agonists; D018118:Chloride Channels; D002712:Chlorides; D000242:Cyclic AMP; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D007545:Isoproterenol; D010636:Phenols; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C505032:CFTR protein, human; C102635:1-ethyl-2-benzimidazolinone; C006780:bisphenol A; D000098826:Bisphenol A Compounds