Schachter E N, Zuskin E, Rienzi N, Goswami S, Maayani S, Wan A E, Castranova V, Siegel P, Whitmer M, Mustajbegovic J
Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Lung. 1998;176(1):35-44. doi: 10.1007/pl00007590.
The effect of paper dust collected at two different locations in a paper recycling plant (PD1 and PD2) on isolated nonsensitized guinea pig tracheal smooth muscle was studied in vitro. Dust extracts were prepared as a 1:10 w/v aqueous solution. Dose-related contractions of guinea pig tracheal rings were elicited with both PD1 and PD2. Pharmacologic studies were performed with atropine (10(-6) M), indometacin (10(-6) M), pyrilamine (10(-6) M), LY171883 (10(-5) M), nordihydroguaiaretic acid (10(-5) M), and TMB8 (10(-5) M). The possible role of endogenous neuropeptides in this constrictor process was studied by depleting neural mediators with capsaicin (5 x 10(-6) M) before challenge with dust extracts. Constrictor effects were partially inhibited by a wide variety of the mediator blocking agents. The effects of both extracts were almost totally inhibited by the anticholinergic agent atropine, suggesting that a principal pathway mediating this response may involve the parasympathetic nervous system. The intracellular calcium-blocking agent TMB8 also induced a reduction of the contractile responses to PD1 and PD2 consistent with the well established role of intracellular calcium in smooth muscle constriction. Pretreatment with capsaicin significantly increased the contractile activity of paper dust extracts but only at the higher doses of these extracts. This suggests that the effect of paper dust is not initiated by the release of mediators stored in sensory nerves but that the prerelease of these mediators may enhance the constrictor effects of these dusts. We suggest that paper dust extracts cause dose-related airway smooth muscle constriction possibly associated with the release of cholinergic as well as other mediators. The constrictor effect does not require tissue presensitization or the release of neuropeptides from sensory nerves.
在体外研究了在一家纸张回收厂两个不同位置收集的纸尘（PD1和PD2）对分离出的未致敏豚鼠气管平滑肌的影响。将粉尘提取物配制成1:10 w/v的水溶液。PD1和PD2均能引起豚鼠气管环剂量相关的收缩。使用阿托品（10(-6) M）、吲哚美辛（10(-6) M）、吡苄明（10(-6) M）、LY171883（10(-5) M）、去甲二氢愈创木酸（10(-5) M）和TMB8（10(-5) M）进行了药理学研究。在用粉尘提取物激发前，通过用辣椒素（5×10(-6) M）消耗神经介质来研究内源性神经肽在这种收缩过程中的可能作用。多种介质阻断剂部分抑制了收缩作用。两种提取物的作用几乎完全被抗胆碱能药物阿托品抑制，这表明介导这种反应的主要途径可能涉及副交感神经系统。细胞内钙阻断剂TMB8也导致对PD1和PD2的收缩反应降低，这与细胞内钙在平滑肌收缩中已确立的作用一致。用辣椒素预处理显著增加了纸尘提取物的收缩活性，但仅在这些提取物的较高剂量时。这表明纸尘的作用不是由感觉神经中储存的介质释放引发的，而是这些介质的预释放可能增强了这些粉尘的收缩作用。我们认为纸尘提取物会引起剂量相关的气道平滑肌收缩，可能与胆碱能以及其他介质的释放有关。收缩作用不需要组织预致敏或感觉神经释放神经肽。
