Kohrogi H, Yamaguchi T, Kawano O, Honda I, Ando M, Araki S
First Department of Internal Medicine, Kumamoto University Medical School, Japan.
Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):636-41. doi: 10.1164/ajrccm/144.3_Pt_1.636.
To study the role of tachykinins and neutral endopeptidase (NEP), an enzyme that degrades tachykinins, in the immune response in the airways of guinea pigs sensitized to ovalbumin (OVA), we examined the bronchial contractile response to OVA by inhibiting NEP in vitro. After incubating bronchial tissues with the NEP inhibitors phosphoramidon and thiorphan, we added 10(-5)% (10 micrograms/ml) OVA. Phosphoramidon and thiorphan (10(-5) M) significantly maintained the contraction that followed the peak contraction. In the next stages of the experiment, when the contraction induced by 10(-5)% OVA reached a plateau and began to relax, we added 10(-5) M phosphoramidon. Phosphoramidon inhibited the relaxation and significantly potentiated the contraction. In tissues treated with 10(-5) M capsaicin to deplete tachykinins, phosphoramidon did not potentiate the OVA-induced contraction, but substance P (10(-6) M) caused contraction. These results suggest that the immune response causes the release of tachykinin-like substances from capsaicin-sensitive nerves to induce bronchial contraction in part. To confirm the mediators that cause the release of the tachykinin-like substances from the bronchus, we also examined whether phosphoramidon potentiates the effect of leukotriene C4 (LTC4), serotonin, histamine, and platelet-activating factor on bronchial contraction. When the contractions induced by these agonists reached a plateau and began to relax, we added phosphoramidon. Phosphoramidon inhibited the relaxation and significantly potentiated the contractile response to 10(-5) M LTC4, and it significantly reduced the relaxing rate of the 10(-6) M serotonin-induced contraction. However, it did not change the effect of histamine and platelet-activating factor.(ABSTRACT TRUNCATED AT 250 WORDS)
为研究速激肽和中性内肽酶（NEP，一种可降解速激肽的酶）在对卵清蛋白（OVA）致敏的豚鼠气道免疫反应中的作用，我们通过体外抑制NEP来检测支气管对OVA的收缩反应。在用NEP抑制剂磷酰胺素和硫磷酰胺素孵育支气管组织后，我们加入10⁻⁵%（10微克/毫升）的OVA。磷酰胺素和硫磷酰胺素（10⁻⁵摩尔）显著维持了继峰值收缩后的收缩。在实验的下一阶段，当由10⁻⁵% OVA诱导的收缩达到平台期并开始松弛时，我们加入10⁻⁵摩尔的磷酰胺素。磷酰胺素抑制了松弛并显著增强了收缩。在用10⁻⁵摩尔辣椒素处理以耗尽速激肽的组织中，磷酰胺素并未增强OVA诱导的收缩，但P物质（10⁻⁶摩尔）引起了收缩。这些结果表明，免疫反应导致辣椒素敏感神经释放速激肽样物质，部分诱导支气管收缩。为证实引起支气管释放速激肽样物质的介质，我们还检测了磷酰胺素是否增强白三烯C4（LTC4）、5-羟色胺、组胺和血小板活化因子对支气管收缩的作用。当这些激动剂诱导的收缩达到平台期并开始松弛时，我们加入磷酰胺素。磷酰胺素抑制了松弛并显著增强了对10⁻⁵摩尔LTC4的收缩反应，且显著降低了10⁻⁶摩尔5-羟色胺诱导收缩的松弛速率。然而，它并未改变组胺和血小板活化因子的作用。（摘要截选至250词）
