Changes in β2-adrenoceptor and other signaling proteins produced by chronic administration of 'β-blockers' in a murine asthma model
Changes in β2-adrenoceptor and other signaling proteins produced by chronic administration of 'β-blockers' in a murine asthma model
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DOI：
10.1016/j.pupt.2007.06.003
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发表时间：
2008-01-01
影响因子：
3.2
通讯作者：
Bond, Richard A.
中科院分区：
文献类型：
--
作者：
Lin, Rui;Peng, Hui;Bond, Richard A.
背景：我们之前曾报道，在哮喘小鼠模型中，某些“β-受体阻滞剂”的长期治疗可降低对乙酰甲胆碱的气道高反应性（AHR）。方法：在用几种β-肾上腺素受体（β-AR）配体治疗的卵清蛋白致敏和卵清蛋白激发的小鼠中，使用强制振荡技术测量气道阻力。我们使用选择性 β(2)-AR 配体 ICI 118,551 和优先 β(1)-AR 配体美托洛尔来研究介导有益作用的受体 SLlhtyj)C。使用免疫荧光评估β-AR的表达。我们使用肺匀浆通过蛋白质印迹评估了几种信号蛋白，并测量了 EP2 和 IP 受体激动剂产生的离体气管的松弛。结果：有四个发现与长期 β 受体阻滞剂治疗后 AHR 降低相关：（1）高选择性 β（2）-AR 拮抗剂/反向激动剂，ICI 118,551 产生支气管保护作用； (2) 长期“β受体阻滞剂”治疗导致β(2)-AR上调； (3)某些参与调节支气管张力的蛋白质的表达减少，即G(i)、磷酸二酯酶4D和磷脂酶C-β1； (4) 对 IP 和 EP2 受体的前列腺素激动剂的支气管扩张反应增强。结论：这些数据表明，在哮喘小鼠模型中，一些与支气管扩张信号增加或支气管收缩信号减少相关的代偿性变化是由长期服用某些“β-受体阻滞剂”引起的。 (C) 2007 Elsevier Ltd. 保留所有权利。
Background: We have previously reported that chronic treatment with certain 'beta-blockers' reduces airway hyperresponsiveness (AHR) to methacholine in a murine model of asthma.Methods: Airway resistance was measured using the forced oscillation technique in ovalbulmin-sensitized and ovalbumin-challenged mice treated with several beta-adrenoceptor (beta-AR) ligands. We used the selective beta(2)-AR ligand ICI 118,551 and the preferential beta(1)-AR ligand metoprolol to investigate the receptor SLlhtyj)C mediating the beneficial effect. Expression of beta-ARs was evaluated using immunofluorescence. We evaluated several signaling proteins by western blot using lung homogenates, and measured the relaxation of the isolated trachea produced by EP2 and IP receptor agonists.Results: Four findings were associated with the decreased AHR after chronic beta-blocker treatment: (1) the highly selective beta(2)-AR antagonist/inverse agonist, ICI 118,551 produced the bronchoprotective effect; (2) beta(2)-AR up-regulation resulted from chronic 'beta-blocker' treatment; (3) reduced expression of certain proteins involved in regulating bronchial tone, namely, G(i), phosphodiesterase 4D and phospholipase C-beta 1; and (4) in enhanced bronchodilatory response to prostanoid agonists for the IP and EP2 receptors.Conclusions: These data suggest that in the murine model of asthma, several compensatory changes associated with either increased bronchodilator signaling or decreased bronchoconstrictive signaling, result from the chronic administration of certain 'beta-blockers'. (C) 2007 Elsevier Ltd. All rights reserved.