Nitric oxide-dependent ethanol stimulation of ciliary motility is linked to cAMP-dependent protein kinase (pka) activation in bovine bronchial epithelium

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Abstract

Background: The first line of protection in the lung from the outside environment is provided by the mucociliary apparatus, which continually clears the airways of inhaled microorganisms, dust, and debris. Because alcohol is known to impair airway host defenses, we have examined the effects of ethanol on mucociliary function. In earlier studies, we found that ethanol rapidly and transiently stimulates ciliary motility through a nitric oxide- dependent mechanism. Because many agonists stimulate ciliary motility through activation of cyclic nucleotide-dependent protein kinases, we hypothesized that ethanol stimulates ciliary motility by activating protein kinases. Methods: Protein kinase activity and ciliary beat frequency (CBF) were assayed in primary cultures of bovine bronchial epithelial cells after exposure to ethanol. Results: Ethanol markedly activated cyclic adenosine monophosphate (cAMP)-dependent protein kinase [protein kinase A (PKA)] at biologically relevant concentrations (20-100 mM), with activation detectable after 15 min and persisting up to 4 hr. Ethanol's PKA activation was blocked by nitric oxide synthase inhibitors, indicating a nitric oxide-dependent pathway, and was also specifically blocked by PKA inhibitors. Ethanol did not directly activate cyclic guanosine monophosphate (cGMP)-dependent protein kinase [protein kinase G (PKG)] in bovine bronchial epithelial cells, but inhibitors of PKG attenuated PKA activation, suggesting a link between PKA activation and PKG activation during ethanol exposure. CBF increased in parallel to PKA activation, suggesting tight coupling between stimulated CBF and PKA activation. Conclusion: We conclude that ethanol stimulates CBF through activating PKA in bovine bronchial epithelial cells and we suggest a cooperative mechanism involving PKA and nitric oxide.

Original languageEnglish (US)
Pages (from-to)1528-1533
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume23
Issue number9
StatePublished - Oct 16 1999

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Keywords

  • Airway Epithelium
  • Ciliary Motility
  • Ethanol
  • Nitric Oxide
  • PKA
  • PKG

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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