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

Rene Schmidt¹ , Petra Staats² , David A Groneberg³ and Ulrich Wagner⁴

¹Department of Anesthesiology, University Medical Center, Hugstetter Strasse 55, D-79106 Freiburg, Germany

²Department of Medicine, Division of Pneumology, University Medical Center, Baldingerstrasse, D-35043 Marburg, Germany

³Institute of Occupational Medicine, Charité – Universitaetsmedizin, Free University and Humboldt University, Augustenburger Platz 1, D-13353 Berlin, Germany

⁴Department of Internal Medicine, Division of Pneumology, Klinik Loewenstein, Geißhoelzle 62, D-74245 Loewenstein, Germany

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Journal of Occupational Medicine and Toxicology 2008, 3:5doi:10.1186/1745-6673-3-5


Published:	20 February 2008

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 ³⁵SO₄labelled 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.