Acrolein-induced smooth muscle hyperresponsiveness and eicosanoid release in excised ferret tracheae.
Acrolein-induced smooth muscle hyperresponsiveness and eicosanoid release in excised ferret tracheae.
复制标题
丙烯醛诱导的平滑肌高反应性和切除的雪貂气管中类二十烷酸的释放。
DOI：
10.1006/taap.1995.1206
复制
发表时间：
1995
影响因子：
3.8
通讯作者：
Ultman,JS
中科院分区：
文献类型：
--
作者：
Ben-Jebria,A;Crozet,Y;Eskew,ML;Rudeen,BL;Ultman,JS
丙烯醛是一种无处不在的有毒空气污染物，会对肺部产生不利影响。为了了解与丙烯醛摄取有关的气道反应性的控制机制，进行了体外实验，将雪貂切除的气管暴露于几种浓度（0-12.5 ppm）的空气中丙烯醛混合物的单向恒流（100 ml/min）中1小时。在暴露过程中，通过对气管入口和出口采集的气体样品进行色谱分析来确定丙烯醛进入气管的摄取。暴露后测量平滑肌收缩力对胆碱（CCh）、乙酰胆碱（ACh）和氯化钾（KCl）的反应，并测定灌注液中释放的类二十烷酸。结果表明，丙烯醛在切除的雪貂气管内的吸收分数强烈依赖于入口浓度，这意味着丙烯醛在气道组织中的扩散和反应过程不是线性的。只有低浓度丙烯醛引起灌注液中暴露气管的类二十烷酸释放增加；可能在较高的暴露浓度下，上皮脱落，大部分二十烷类细胞丢失。丙烯醛虽然没有改变平滑肌对KCl的反应，但却增加了对CCh和ACh的收缩反应，表明改变了雪貂气管平滑肌的药物力学而不是机电耦合；因此，这种高反应性更有可能主要是通过细胞内Ca2+储存的动员而不是通过电压依赖性通道增加细胞外Ca2+的流入。
Acrolein is a ubiquitous toxic air pollutant that can have adverse lung effects. To understand the mechanism governing airway reactivity in relation to acrolein uptake, in vitro experiments were conducted in which excised tracheae from ferrets were exposed for 1 hr to a unidirectional constant flow (100 ml/min) of an acrolein-in-air mixture at several concentrations (0-12.5 ppm). During exposure, acrolein uptake into the trachea was determined by a chromatographic analysis of gas samples taken at the entrance and at the exit of the trachea. Smooth muscle contractility in response to carbachol (CCh), acetylcholine (ACh), and potassium chloride (KCl) was measured following exposure, and eicosanoids released in the perfusate baths were assayed. The results indicate that the fractional uptake into an excised ferret trachea was strongly dependent on inlet concentration, implying that diffusion and reaction processes of acrolein in airway tissue are not linear. Only the low concentration of acrolein caused an increase of eicosanoid release from the exposed tracheae in the perfusate bath; it is possible that, at higher exposure concentration, the epithelium was sloughed off and most of the eicosanoids were lost. Although acrolein did not alter smooth muscle response to KCl, it did increase the contractile responses to CCh and ACh, suggesting an alteration in the pharmacomechanical but not the electromechanical coupling of ferret tracheal smooth muscle; therefore, it is more likely that this hyperresponsiveness occurs primarily by a mobilization of intracellular Ca2+stores rather than by an increased influx of extracellular Ca2+through voltage-dependent channels.