Smith J A, Frazer D G, Fedan J S
Department of Pharmacology and Toxicology, West Virginia University, Morgantown.
J Pharmacol Exp Ther. 1993 Feb;264(2):683-8.
Chest tightness may occur after inhalation of cotton dust. To understand the origins of this symptom of byssinosis, we exposed guinea pigs to respirable cotton dust and determined whether the resulting pulmonary obstruction was associated with alterations in the in vitro reactivity of the trachea to methacholine. The isolated, perfused trachea preparation was utilized because it allows a comparison of airway smooth muscle responses to drugs after they are applied separately to the mucosal or serosal surfaces. In epithelium-containing control tracheae, mucosally applied methacholine was less potent and elicited smaller maximum contractile responses than those obtained when it was applied to the serosal compartment. After a 6-h inhalation exposure to 30 mg/m3 respirable cotton dust, the mucosal maximum response to methacholine was substantially increased immediately (0 h) after the end of the exposure, but it was decreased 18 h postexposure. A dust level of 10 mg/m3 produced modest increases in the mucosal maximum responses at both postexposure periods, elevating them to the magnitude of the extraluminal maximum response. The potency of serosally applied methacholine was not affected by any cotton dust exposure. Mechanical epithelium removal increased mucosal reactivity to the serosal level in both control and cotton (30 mg/m3)-exposed groups, and abolished the effects of dust on mucosal reactivity to methacholine. Our findings suggest that the modulatory effect of the epithelium may be inhibitory or excitatory. The balance between the two influences may be altered by inhaled cotton dust.
吸入棉尘后可能会出现胸闷。为了了解棉屑沉着病这种症状的起因,我们将豚鼠暴露于可吸入棉尘中,并确定由此产生的肺阻塞是否与气管对乙酰甲胆碱的体外反应性改变有关。使用离体灌注气管标本是因为它能比较药物分别作用于黏膜或浆膜表面后气道平滑肌的反应。在含有上皮的对照气管中,黏膜给予乙酰甲胆碱时效力较低,引起的最大收缩反应比给予浆膜腔时小。在吸入30mg/m³可吸入棉尘6小时后,暴露结束后立即(0小时)黏膜对乙酰甲胆碱的最大反应大幅增加,但在暴露后18小时降低。10mg/m³的粉尘水平在两个暴露后时间段都使黏膜最大反应适度增加,使其达到管腔外最大反应的程度。浆膜给予乙酰甲胆碱的效力不受任何棉尘暴露的影响。机械去除上皮可增加对照和棉尘(30mg/m³)暴露组黏膜对浆膜水平的反应性,并消除粉尘对黏膜对乙酰甲胆碱反应性的影响。我们的研究结果表明,上皮的调节作用可能是抑制性的或兴奋性的。吸入棉尘可能会改变这两种影响之间的平衡。