Vol. 302, Issue 1, 80-87, July 2002

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 and Kenichi Yamaki

Division II (Respiratory Division), Internal Medicine II, University of Nagoya School of Medicine, Nagoya, Japan

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 (I_sc) more potently than 17-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 I_sc 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 Cl current. Bisphenol A, but neither 17-estradiol nor tamoxifen, interrupted the charybdotoxin-sensitive component of I_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 Cl secretion through inhibition of both cAMP- and Ca²⁺-activated K⁺ channels on the basolateral membrane, interacting from the cytosolic surface in Calu-3 cells.