2004年2月
Effects of fluoranthene, a polycyclic aromatic hydrocarbon, on cAMP-dependent anion secretion in human airway epithelia
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
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- 巻
- 308
- 号
- 2
- 開始ページ
- 651
- 終了ページ
- 657
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1124/jpet.103.059089
- 出版者・発行元
- AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
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 (I-sc). However, fluoranthene (1-100 muM) 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 hIK-1 channel blocker). Fluoranthene gradually augmented the ChTx-sensitive K+ current (I-K) 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 hIK-1-dependent I-K 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 hIK-1 channel, whose sensitivity to protein kinase A may be up-regulated by the sustained [Ca2+](i) elevation produced by this chemical.
- リンク情報
- ID情報
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- DOI : 10.1124/jpet.103.059089
- ISSN : 0022-3565
- Web of Science ID : WOS:000188467800032