Bisphenol A inhibits Cl- secretion by inhibition of basolateral K+ conductance in human airway epithelial cells

Yasushi Ito, Shinji Sato, Masami Son, Masashi Kondo, Hiroaki Kume, Kenzo Takagi, Kenichi Yamaki

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 (IC50 = 60 μM, for 30 min) prevented isoproterenol (10 nM)-generated short-circuit current (Isc) more potently than 17 β-estradiol or tamoxifen (IC50 = 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 Isc responses to forskolin (10 μM) 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 μM) and insensitive to charybdotoxin (100 nM), without affecting the apical CI- current. Bisphenol A, but neither 17 β-estradiol nor tamoxifen, interrupted the charybdotoxin-sensitive component of /sc stimulated by 1-ethyl-2-benzimidazolinone (1-EBIO; 500 μM). 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 μM; 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 CI- secretion through inhibition of both cAMP- and Ca2+-activated K+ channels on the basolateral membrane, interacting from the cytosolic surface in Calu-3 cells.

Original languageEnglish
Pages (from-to)80-87
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume302
Issue number1
DOIs
Publication statusPublished - 04-07-2002

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Epithelial Cells
Isoproterenol
Charybdotoxin
8-Bromo Cyclic Adenosine Monophosphate
Tamoxifen
Inhibitory Concentration 50
Estradiol
Clotrimazole
bisphenol A
Calcium-Activated Potassium Channels
Nystatin
Membranes
Benzoates
Colforsin
Estrogens
Hormones
Health
1-ethyl-2-benzimidazolinone

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Ito, Yasushi ; Sato, Shinji ; Son, Masami ; Kondo, Masashi ; Kume, Hiroaki ; Takagi, Kenzo ; Yamaki, Kenichi. / Bisphenol A inhibits Cl- secretion by inhibition of basolateral K+ conductance in human airway epithelial cells. In: Journal of Pharmacology and Experimental Therapeutics. 2002 ; Vol. 302, No. 1. pp. 80-87.
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Bisphenol A inhibits Cl- secretion by inhibition of basolateral K+ conductance in human airway epithelial cells. / Ito, Yasushi; Sato, Shinji; Son, Masami; Kondo, Masashi; Kume, Hiroaki; Takagi, Kenzo; Yamaki, Kenichi.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 302, No. 1, 04.07.2002, p. 80-87.

Research output: Contribution to journalArticle

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AU - Sato, Shinji

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AB - 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 (IC50 = 60 μM, for 30 min) prevented isoproterenol (10 nM)-generated short-circuit current (Isc) more potently than 17 β-estradiol or tamoxifen (IC50 = 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 Isc responses to forskolin (10 μM) 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 μM) and insensitive to charybdotoxin (100 nM), without affecting the apical CI- current. Bisphenol A, but neither 17 β-estradiol nor tamoxifen, interrupted the charybdotoxin-sensitive component of /sc stimulated by 1-ethyl-2-benzimidazolinone (1-EBIO; 500 μM). 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 μM; 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 CI- secretion through inhibition of both cAMP- and Ca2+-activated K+ channels on the basolateral membrane, interacting from the cytosolic surface in Calu-3 cells.

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