慢性系统性管理氟替卡松加沙美特罗老鼠促进肺β(2)肾上腺素能受体脱敏和G (sα)的下调。
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芬尼PA,唐纳利勒,Belvisi毫克,壮族TT,博雷尔M,哈里斯,麦JC,射手C,巴恩斯PJ,爱德考克IM, Giembycz MA
慢性系统性管理氟替卡松加沙美特罗老鼠促进肺β(2)肾上腺素能受体脱敏和G (sα)的下调。
Br J杂志。2001年3月,132 (6):1261 - 70。
- PubMed ID
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11250877 (在PubMed]
- 文摘
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1。本研究的目的是审查的影响长期输液的长效β受体激动剂氟替卡松加沙美特罗在肺(2)肾上腺素能受体功能Sprague-Dawley老鼠体内,并阐明任何改变状态的分子基础。2。系统性的老鼠与氟替卡松加沙美特罗7天妥协的能力氟替卡松加沙美特罗和前列腺素E(2)(铂族元素(2)),鉴于静脉强烈的路线,来防止ACh-induced支气管狭窄治疗的老鼠相比与车辆相同。3所示。β(1)-和β(2)肾上腺素受体密度显著降低肺膜是从salmeterol-treated动物,这是与氟替卡松加沙美特罗——受损和铂族元素(2)全身环腺苷酸体外积累。4所示。三种变体的G (sα)迁移为42,44岁和52 kDa肽在SDS聚丙烯酰胺凝胶检测肺膜由两组老鼠,但每个同种型的强度明显降低大鼠接受氟替卡松加沙美特罗。5。胞质的活动,但不是膜相关蛋白receptor-coupled激酶升高在salmeterol-treated老鼠vehicle-treated相比,动物的肺。 6. The ability of salmeterol, administered systemically, to protect the airways of untreated rats against ACh-induced bronchoconstriction was short-acting (t(off) approximately 45 min), which contrasts with its long-acting nature when given to asthmatic subjects by inhalation. 7. These results indicate that chronic treatment of rats with salmeterol results in heterologous desensitization of pulmonary G(s)-coupled receptors. In light of previous data obtained in rats treated chronically with salbutamol, we propose that a primary mechanism responsible for this effect is a reduction in membrane-associated G(s alpha). The short-acting nature of salmeterol, when administered systemically, and the reduction in beta-adrenoceptor number may be due to metabolism to a biologically-active, short-acting and non-selective beta-adrenoceptor agonist.