Tudoric N, Coon R L, Flynn N M, Bosnjak Z J
Department of Anesthesiology, Zablocki Veterans Administration Medical Center, Milwaukee, Wisc.
Int Arch Allergy Immunol. 1993;100(2):170-7. doi: 10.1159/000236405.
To determine whether tachykinins participate in antigen-induced constriction of tracheal smooth muscle, we examined the effects of a neutral endopeptidase inhibitor, phosphoramidon, the tachykinin antagonist (D-Pro4, D-Trp7,9,10)-substance P(4-11), and capsaicin-induced tachykinin depletion on the responses to antigen in tracheal rings from ovalbumin-sensitized guinea pigs. In these preparations, the antigen (ovalbumin, 0.1 microgram/ml) produced reproducible and durable constriction of tracheal smooth muscle. Incubation with phosphoramidon (10 min, 10 microM) prior to antigen challenge significantly augmented the magnitude of ovalbumin-induced constriction by 22% after 30 min and by 31% after 45 min. The addition of phosphoramidon at the plateau level of antigen-induced constriction produced a similar, significant increase in the magnitude of the constriction. Following incubation with tachykinin antagonist (D-Pro4,D-Trp7,9,10)-substance P(4-11) (5 microM), the contractile response of the tracheal rings to the antigen was not altered. Furthermore, the addition of phosphoramidon (10 microM) did not significantly affect this contraction. Similarly, neither tachykinin antagonist nor phosphoramidon altered the ovalbumin-induced constriction of the tracheal rings from capsaicin-treated guinea pigs. Based on these findings, we hypothesize that tachykinins or similar broncho-constricting neutral endopeptidase substrates were released from tachykinin-containing nerve endings during immediate hypersensitivity reaction in airways, manifesting a modest and delayed constrictive effect. Following alteration of endopeptidase activity, these substances could modulate the anaphylactic constriction of the airway smooth muscle.
为了确定速激肽是否参与抗原诱导的气管平滑肌收缩，我们研究了中性内肽酶抑制剂磷酰胺素、速激肽拮抗剂（D-脯氨酸4、D-色氨酸7,9,10）-P物质（4-11）以及辣椒素诱导的速激肽耗竭对卵清蛋白致敏豚鼠气管环对抗原反应的影响。在这些制剂中，抗原（卵清蛋白，0.1微克/毫升）可引起气管平滑肌可重复且持久的收缩。在抗原攻击前用磷酰胺素（10分钟，10微摩尔）孵育，30分钟后卵清蛋白诱导的收缩幅度显著增加22%，45分钟后增加31%。在抗原诱导收缩的平台期加入磷酰胺素，收缩幅度也有类似的显著增加。用速激肽拮抗剂（D-脯氨酸4、D-色氨酸7,9,10）-P物质（4-11）（5微摩尔）孵育后，气管环对抗原的收缩反应未改变。此外，加入磷酰胺素（10微摩尔）对这种收缩也没有显著影响。同样，速激肽拮抗剂和磷酰胺素都没有改变辣椒素处理的豚鼠气管环对卵清蛋白的收缩。基于这些发现，我们推测在气道速发型超敏反应期间，速激肽或类似的支气管收缩性中性内肽酶底物从含速激肽的神经末梢释放，表现出适度且延迟的收缩作用。在内肽酶活性改变后，这些物质可调节气道平滑肌的过敏收缩。
