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Key results: Pre-incubation of neutrophils with montelukast resulted in dose-related inhibition of the generation of reactive oxygen species and leukotriene B4 by chemoattractant-activated neutrophils, as well as release of elastase, all of which were maximal at 2 mmol·L-1 (mean percentages of the control values of 30 1, 12 3 and 21 3 respectively; P < 0.05). From a mechanistic perspective, treatment of chemoattractant-activated neutrophils with montelukast resulted in signiﬁcant reduc-
tions in both post-peak cytosolic Ca2+ concentrations and store-operated Ca2+ inﬂux. These montelukast-mediated alterations in Ca2+ handling by the cells were associated with a signiﬁcant elevation in basal cAMP levels, which resulted from inhibition of cyclic nucleotide phosphodiesterases.
Conclusions and implications: Montelukast, primarily a cysteinyl leukotriene (CysLT1) receptor antagonist, exhibited previously undocumented, secondary, neutrophil-directed anti-inﬂammatory properties, which appeared to be cAMP-dependent.

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hljmmj: 金幣+10, 翻譯EPI+1, ★★★★★最佳答案 2016-01-04 09:01:20

主要結(jié)果：將中性粒細(xì)胞與孟魯司特預(yù)培養(yǎng)導(dǎo)致劑量相關(guān)地抑制化學(xué)趨化劑激活中性粒細(xì)胞活性氧簇和白三烯B4的產(chǎn)生及彈性蛋白酶的釋放，所有值均在2 mmol·L-1達(dá)高峰（對(duì)照值的平均百分率分別為 30.1, 12.3 和 21.3; P < 0.05)。從機(jī)理上看，化學(xué)趨化劑激活的中性粒細(xì)胞經(jīng)孟魯斯特處理導(dǎo)致峰后細(xì)胞質(zhì)鈣離子濃度和鈣池調(diào)控鈣離子內(nèi)流均顯著減少。這些由孟魯司特介導(dǎo)的細(xì)胞對(duì)鈣離子處理能力的改變與環(huán)核苷酸磷酸二酯酶抑制引起cAMP基礎(chǔ)水平顯著升高有關(guān)。
結(jié)論及含意：首先，孟魯司特作為半胱氨酰白三烯 (CysLT1)受體拮抗劑先前未有報(bào)道，其次，對(duì)中性粒細(xì)胞的抗炎癥特性表現(xiàn)為 cAMP依賴性。

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2樓2015-12-31 01:40:44

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