孟鲁司特钠对血小板激活因子和激肽诱导的大鼠黏液分泌的影响。

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

机构信息

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

出版信息

J Occup Med Toxicol. 2008 Feb 20;3:5. doi: 10.1186/1745-6673-3-5.

DOI:10.1186/1745-6673-3-5

PMID:18289370

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2278150/

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.

摘要

背景

血小板激活因子和速激肽（P 物质、神经激肽 A、神经激肽 B）是导致不同类型呼吸道疾病（包括急性和慢性哮喘）气道分泌物增加的重要介质。白三烯受体拮抗剂被推荐作为该病的附加治疗药物。半胱氨酸白三烯-1 受体拮抗剂孟鲁司特在过去几年中已用于临床哮喘治疗。除了其对支气管收缩的抑制作用外，人们对其对气道分泌物的影响知之甚少。因此，本研究旨在评估孟鲁司特对血小板激活因子和速激肽诱导的气管分泌活性的影响。

方法

采用改良 Ussing 室技术，通过定量分泌的 35SO4 标记的粘蛋白大分子来评估孟鲁司特对血小板激活因子和速激肽诱导的气管分泌活性的影响。

结果

血小板激活因子能强烈刺激气道分泌，这种分泌被血小板激活因子受体拮抗剂 WEB 2086 和孟鲁司特完全抑制。相比之下，孟鲁司特对速激肽诱导的气管分泌活性没有影响。

结论

孟鲁司特通过半胱氨酸白三烯-1 受体拮抗作用逆转了血小板激活因子的促分泌作用，其程度与特异性血小板激活因子拮抗剂 WEB 2086 相同，但对速激肽引起的气管分泌没有影响。这些结果表明孟鲁司特在血小板激活因子诱导的气道分泌活性的信号转导途径中起作用，并可能进一步解释半胱氨酸白三烯-1 受体拮抗剂的有益特性。