Effects of Fluoranthene, a Polycyclic Aromatic Hydrocarbon, on cAMP-Dependent Anion Secretion in Human Airway Epithelia

Yasushi Ito, Masami Son, Shinji Sato, Takamasa Ohashi, Masashi Kondo, Kaoru Shimokata, Hiroaki Kume

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)651-657
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume308
Issue number2
DOIs
Publication statusPublished - 01-02-2004

Fingerprint

Polycyclic Aromatic Hydrocarbons
Anions
Epithelium
8-Bromo Cyclic Adenosine Monophosphate
ellipticine
Isoproterenol
Charybdotoxin
Benzo(a)pyrene
Ion Transport
Colforsin
Cyclic AMP-Dependent Protein Kinases
fluoranthene
Respiratory System
Inhalation
Lung
Membranes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Ito, Yasushi ; Son, Masami ; Sato, Shinji ; Ohashi, Takamasa ; Kondo, Masashi ; Shimokata, Kaoru ; Kume, Hiroaki. / Effects of Fluoranthene, a Polycyclic Aromatic Hydrocarbon, on cAMP-Dependent Anion Secretion in Human Airway Epithelia. In: Journal of Pharmacology and Experimental Therapeutics. 2004 ; Vol. 308, No. 2. pp. 651-657.
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Effects of Fluoranthene, a Polycyclic Aromatic Hydrocarbon, on cAMP-Dependent Anion Secretion in Human Airway Epithelia. / Ito, Yasushi; Son, Masami; Sato, Shinji; Ohashi, Takamasa; Kondo, Masashi; Shimokata, Kaoru; Kume, Hiroaki.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 308, No. 2, 01.02.2004, p. 651-657.

Research output: Contribution to journalArticle

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AU - Ito, Yasushi

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