Airway responses to aerosolized brevetoxins in an animal model of asthma

William M. Abraham, Andrea J. Bourdelais, Juan R. Sabater, Ashfaq Ahmed, Troy A. Lee, Irakli Serebriakov, Daniel G. Baden

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Florida red tide brevetoxins are sodium channel neurotoxins produced by the dinoflagellate Karenia brevis. When aerosolized, the toxin causes airway symptoms in normal individuals and patients with airway disease, but systematic exposures to define the pulmonary consequences and putative mechanisms are lacking. Here we report the effects of airway challenges with lysed cultures of Karenia brevis (crude brevetoxin), pure brevetoxin-2, brevetoxin-3, and brevetoxin-tbm (brevetoxin-2 minus the side chain) on pulmonary resistance and tracheal mucus velocity, a marker of mucociliary clearance, in allergic and nonallergic sheep. Picogram concentrations of toxin caused bronchoconstriction in both groups of sheep. Brevetoxin-tbm was the least potent, indicating the importance of the side chain for maximum effect. Both histamine H1- and cholinergic-mediated pathways contributed to the bronchoconstriction. A synthetic antagonist, β-naphthoyl-brevetoxin-3, and brevenal, a natural antagonist, inhibited the bronchoconstriction. Only crude brevetoxin and brevetoxin-3 decreased tracheal mucus velocity; both antagonists prevented this. More importantly, picomolar concentrations of the antagonists alone improved tracheal mucus velocity to the degree seen with mM concentrations of the sodium channel blocker amiloride. Thus, Karenia brevis, in addition to producing toxins that adversely affect the airways, may be a source of agents for treating mucociliary dysfunction.

Original languageEnglish (US)
Pages (from-to)26-34
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Volume171
Issue number1
DOIs
StatePublished - Jan 1 2005

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Keywords

  • Bronchoconstriction
  • Mucus transport
  • Natural therapies

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Abraham, W. M., Bourdelais, A. J., Sabater, J. R., Ahmed, A., Lee, T. A., Serebriakov, I., & Baden, D. G. (2005). Airway responses to aerosolized brevetoxins in an animal model of asthma. American journal of respiratory and critical care medicine, 171(1), 26-34. https://doi.org/10.1164/rccm.200406-735OC