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

Schmidt R, Staats P, Groneberg DA, Wagner U - J Occup Med Toxicol (2008)

Bottom Line: Leukotriene receptor antagonists are recommended as add-on therapy for this disease.Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions.In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, Division of Pneumology, Klinik Loewenstein, Geißhoelzle 62, D-74245 Loewenstein, Germany. ulrich.wagner@klinik-loewenstein.de.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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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.

Mentions: Figure 2 shows the influence of the cys-LT1 receptor antagonist montelukast on PAF induced tracheal secretory activity. PAF application (100 μM) led to an increase of mucus secretion up to 205 ± 49% of baseline levels. The addition of montelukast (10 μM) to the culture medium had no significant effect on the secretion levels (95 ± 6%). Combination of PAF (100 μM) and montelukast (10 μM) completely blocked the secretagogue effect observed under PAF application alone (94 ± 5%).


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

Schmidt R, Staats P, Groneberg DA, Wagner U - J Occup Med Toxicol (2008)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2278150&req=5

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.
Mentions: Figure 2 shows the influence of the cys-LT1 receptor antagonist montelukast on PAF induced tracheal secretory activity. PAF application (100 μM) led to an increase of mucus secretion up to 205 ± 49% of baseline levels. The addition of montelukast (10 μM) to the culture medium had no significant effect on the secretion levels (95 ± 6%). Combination of PAF (100 μM) and montelukast (10 μM) completely blocked the secretagogue effect observed under PAF application alone (94 ± 5%).

Bottom Line: Leukotriene receptor antagonists are recommended as add-on therapy for this disease.Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions.In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, Division of Pneumology, Klinik Loewenstein, Geißhoelzle 62, D-74245 Loewenstein, Germany. ulrich.wagner@klinik-loewenstein.de.

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.

No MeSH data available.


Related in: MedlinePlus