Ethanol increases phosphodiesterase 4 activity in bovine bronchial epithelial cells

Ethanol exposure in airway epithelium increases cyclic AMP (cAMP)–dependent protein kinase (PKA) activity. Activation of PKA and cyclic guanosine monophosphate (cGMP)–dependent protein kinase (PKG) has been shown to increase ciliary beat frequency (CBF) in bovine bronchial epithelial cells (BBECs)....

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Bibliographic Details
Published in:Alcohol (Fayetteville, N.Y.) N.Y.), 2003-08, Vol.31 (1), p.31-38
Main Authors: Forgèt, Mary A., Sisson, Joseph H., Spurzem, John R., Wyatt, Todd A.
Format: Article
Language:English
Subjects:
3',5'-Cyclic-AMP Phosphodiesterases - metabolism
Airway epithelium
Alcoholism
Alcoholism and acute alcohol poisoning
Animals
Biological and medical sciences
Bronchi - drug effects
Bronchi - enzymology
cAMP
Cattle
Cells, Cultured
Cilia - drug effects
Cilia - enzymology
Cyclic AMP - metabolism
Cyclic Nucleotide Phosphodiesterases, Type 4
Dose-Response Relationship, Drug
Enzyme Activation - drug effects
Enzyme Activation - physiology
Ethanol
Ethanol - pharmacology
Fetal alcohol syndrome
Kinases
Lung
Lung diseases
Medical sciences
Motility
Nitric oxide
PDE4
Phosphodiesterase
phosphodiesterase 4
PKA
Proteins
Respiratory Mucosa - drug effects
Respiratory Mucosa - enzymology
Studies
Toxicology
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Summary:Ethanol exposure in airway epithelium increases cyclic AMP (cAMP)–dependent protein kinase (PKA) activity. Activation of PKA and cyclic guanosine monophosphate (cGMP)–dependent protein kinase (PKG) has been shown to increase ciliary beat frequency (CBF) in bovine bronchial epithelial cells (BBECs). We have shown that biologically relevant concentrations of ethanol stimulate increases in CBF in a nitric oxide–dependent manner, mediated through elevated cAMP levels and subsequent PKA activation. This ethanol-driven rapid and transient increase in CBF occurs 15 to 30 min after exposure to 100 mM ethanol. However, after prolonged exposure to 100 mM ethanol (≥6 h), CBF and the catalytic activity of PKA return to baseline levels. We hypothesize that cyclic nucleotide–dependent phosphodiesterase (PDE) activity attenuates the duration of ethanol-stimulated ciliary motility. The effect of ethanol on the PDE activity in BBECs was determined through direct assay of catalytic activity. When BBECs were incubated with 100 mM ethanol, significant increases in cAMP levels occurred within 1 h, with corresponding increases in PKA activity. Treatment of BBECs with 100 mM ethanol increased cAMP–PDE activity significantly by 4 h. 3-Isobutyl-1-methylxanthine, Ro 20-1724, and rolipram inhibited ethanol-stimulated cAMP–PDE activity. These agents inhibited ethanol-stimulated cAMP–PDE activity and increased the magnitude of ethanol-stimulated PKA activity observed under the same conditions. These findings support the idea that acute exposure (
ISSN:0741-8329
1873-6823
DOI:10.1016/j.alcohol.2003.06.005