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. 2008 Feb 20:3:5.
doi: 10.1186/1745-6673-3-5.

Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

Rene Schmidt  1 , Petra Staats, David A Groneberg, Ulrich Wagner
Affiliations

Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

Rene Schmidt et al. J Occup Med Toxicol. .

Abstract

Background: 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. 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.

Methods: The 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.

Results: Platelet 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.

Conclusion: Cys-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.

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Figures

Figure 1
Figure 1
Effects of WEB 2086 on platelet activating factor (PAF) induced tracheal secretory activity in the rat. Data are expressed as mean ± SEM for n = 5 animals per group. *P < 0.05 versus respective baseline secretion values (within each group); #P < 0.05 versus PAF.
Figure 2
Figure 2
Effects of montelukast on platelet activating factor (PAF) induced tracheal secretory activity in the rat. Data are expressed as mean ± SEM for n = 5 animals per group. *P < 0.05 versus respective baseline secretion values (within each group); #P < 0.05 versus PAF.
Figure 3
Figure 3
Effects of montelukast on tachykinin (substance P (A), neurokinin A (B), neurokinin B (C)) induced tracheal mucus secretion in the rat. Data are expressed as mean ± SEM for n = 5 animals per group. *P < 0.05 versus respective baseline secretion values (within each group); #P < 0.05 versus montelukast.
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