The human respiratory tract is constantly exposed to polycyclic aromatic hydrocarbons (PAHs) through inhalation of atmospheric pollutants. We examined the effects of three PAHs (benzo[a]pyrene), anthracene, and fluoranthene) on the airway ion transport, which is essential for lung defense and normal airway function, using human airway epithelia (Calu-3). These three PAHs had no significant effect on the basal short-circuit current (ISC). However, fluoranthene (1-100 μM) applied in the apical compartment potentiated I SC in response to cAMP-related agents (isoproterenol, forskolin, and 8-bromo-cAMP). The effects of fluoranthene were unaffected by ellipticine, a PAH receptor antagonist. Estimation of the anionic composition of I SC revealed that isoproterenol increased both HCO3 - and Cl- transport in the control, whereas it potentiated only Cl- transport in the presence of fluoranthene. The fluoranthene-induced modulations of these anion transporters were counteracted by charybdotoxin (ChTx, a hlK-1 channel blocker). Fluoranthene gradually augmented the ChTx-sensitive K+ current (IK) across the basolateral membrane, accompanied by a sustained increase in the cytosolic Ca2+ concentration ([Ca2+]i). In the presence of fluoranthene, however, a much larger hlK-1-dependent IK was identified by the application of 8-bromo-cAMP without concomitant elevation of [Ca2+]i. These results suggest that fluoranthene switches from cAMP-dependent HCO3- secretion to Cl- secretion through the hlK-1 channel, whose sensitivity to protein kinase A may be up-regulated by the sustained [Ca2+]i elevation produced by this chemical.
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 01-02-2004|
All Science Journal Classification (ASJC) codes
- Molecular Medicine