Smoking particles enhance endothelin A and endothelin B receptor-mediated contractions by enhancing translation in rat bronchi.
Smoking particles enhance endothelin A and endothelin B receptor-mediated contractions by enhancing translation in rat bronchi.
复制标题
吸烟颗粒通过增强大鼠支气管中的翻译来增强内皮素A和内皮素B受体介导的收缩。
DOI：
10.1186/1471-2466-6-6
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发表时间：
2006-03-15
影响因子：
3.1
通讯作者：
Edvinsson, Lars
中科院分区：
文献类型：
--
作者：
Granstrom, Bengt W;Xu, Cang-Bao;Nilsson, Elisabeth;Vikman, Petter;Edvinsson, Lars
已知吸烟会引起支气管的慢性炎症变化，并导致气道高反应性，如支气管哮喘。为了研究吸烟对大鼠气道内皮素系统的影响，将大鼠支气管段分别暴露于香烟烟雾中的DMSO可溶性吸烟颗粒（DSP）、尼古丁和DMSO。在单独存在或不存在DSP、尼古丁或DMSO的情况下培养分离的大鼠支气管节段24小时。用敏感的肌电描记器研究了对sarafotoxin 6c（一种ETB受体的选择性激动剂）和内皮素-1（一种ETA和ETB受体激动剂）的收缩反应。在ET-1导入之前，用S6 c使ETB受体脱敏。观察到的剩余收缩性被认为是选择性激活ETA受体的结果。采用实时定量PCR分析ETA和ETB受体mRNA表达。ETA和ETB受体的位置和浓度通过免疫组织化学和共聚焦显微镜与选择性抗体孵育过夜后进行了研究。在与DSP一起培养24小时后，支气管段显示出由ETA和ETB受体介导的增加的收缩性，而与尼古丁一起培养它们不影响它们的收缩性。放线菌酮治疗，翻译抑制剂，他们的收缩性的上调钝化。通过暴露于DMSO或单独暴露于尼古丁，ETA和ETB受体mRNA的表达没有显著变化，尽管免疫组织化学显示在DSP存在下孵育后平滑肌中ETA和ETB受体明显增加。总的来说，这被视为翻译机制的存在。当暴露于DSP时，大鼠支气管的收缩性增加似乎是由于翻译机制。
Smoking is known to cause chronic inflammatory changes in the bronchi and to contribute to airway hyper-reactivity, such as in bronchial asthma. To study the effect of smoking on the endothelin system in rat airways, bronchial segments were exposed to DMSO-soluble smoking particles (DSP) from cigarette smoke, to nicotine and to DMSO, respectively. Isolated rat bronchial segments were cultured for 24 hours in the presence or absence of DSP, nicotine or DMSO alone. Contractile responses to sarafotoxin 6c (a selective agonist for ETB receptors) and endothelin-1 (an ETA and ETB receptor agonist) were studied by use of a sensitive myograph. Before ET-1 was introduced, the ETB receptors were desensitized by use of S6c. The remaining contractility observed was considered to be the result of selective activation of the ETA receptors. ETA and ETB receptor mRNA expression was analyzed using real-time quantitative PCR. The location and concentration of ETA and ETB receptors were studied by means of immunohistochemistry together with confocal microscopy after overnight incubation with selective antibodies. After being cultured together with DSP for 24 hours the bronchial segments showed an increased contractility mediated by ETA and ETB receptors, whereas culturing them together with nicotine did not affect their contractility. The up-regulation of their contractility was blunted by cycloheximide treatment, a translational inhibitor. No significant change in the expression of ETA and ETB receptor mRNA through exposure to DMSO or to nicotine exposure alone occurred, although immunohistochemistry revealed a clear increase in ETA and ETB receptors in the smooth muscle after incubation in the presence of DSP. Taken as a whole, this is seen as the presence of a translation mechanism. The increased contractility of rat bronchi when exposed to DSP appears to be due to a translation mechanism.