Abstract
BackgroundPlatelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B) are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity.MethodsThe effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique.ResultsPlatelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity.ConclusionCys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.
Highlights
Platelet activating factor and tachykinins are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma
Journal of Occupational Medicine and Toxicology 2008, 3:5 http://www.occup-med.com/content/3/1/5 of peptides which are released from airway nerves upon stimulation [3]
We have previously demonstrated that tachykinins are potent inducers of tracheal mucus secretion in the rat [46]
Summary
Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B) are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. It has been postulated that PAF has the potential to generate bioactive lipids via the 5-lipoxygenase pathway, which represents a possible mechanism mediating its secretagogue properties [10,11,12] In this regard, Goswami et al could show that PAF stimulates the secretion of respiratory glycoconjugates from human airways in culture, which was totally inhibited by the experimentally used competitive leukotriene D4 antagonist LY 171883 [13]. The effect of clinically available cysteinyl-leukotriene-1 (cys-LT1) antagonists (montelukast, zafirlukast, or pranlukast) on PAF- or tachykinin induced secretory activity in the airways has never been evaluated. It was the aim of this study to investigate the effects of montelukast on PAF- and tachykinin induced tracheal mucus secretion
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