速激肽在蒸馏水诱导的豚鼠支气管收缩中的作用。

Fujimura M, Amemiya T, Myou S, Mizuguchi M, Ishiura Y, Sasaki S, Matsuda T

The Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.

Clin Exp Allergy. 1998 Jul;28(7):893-900. doi: 10.1046/j.1365-2222.1998.00320.x.

BACKGROUND

An inhalation of ultrasonically nebulized distilled water (UNDW) induces bronchoconstriction only in asthmatics, but the mechanism underlying the response is not fully understood. We recently showed that bronchoconstriction occurs immediately after UNDW is inhaled 20min after an aerosolized antigen challenge in passively sensitized guinea-pigs.

OBJECTIVE

This study was conducted to examine the role of tachykinins in this response.

METHODS

Passively sensitized animals were anaesthetized and artificially ventilated, and changes in pressure at the airway opening (Pao) were measured as an overall index of airway narrowing. A tachykinin NK1 and NK2 dual receptor antagonist, FK224, and a tachykinin NK1 selective antagonist, FK888, were intravenously administered 15 min after the antigen challenge. The effects of capsaicin desensitization and a neutral endopeptidase inhibitor, phosphoramidon, were also examined.

RESULTS

FK224 and FK888 significantly (P < 0.05 and P < 0.05, respectively) reduced the time course curve of the increase in Pao caused by UNDW inhalation in a dose-dependent manner. The percentage increase in Pao from the preantigen challenge value at 1 min after the UNDW inhalation was 267.4+/-17.1, 358.0+/-33.7 and 412.4+/-27.6% with 10 mg/kg of FK224, 1.0 mg/kg of FK224 and vehicle, respectively, (P<0.01 between 10 mg/kg of FK224 and vehicle) and the value was 254.4+/-48.5% with 10 mg/kg of FK888, 327.1+/-57.6% with 1.0 mg/kg of FK888 and 418.5+/-39.0% with vehicle, respectively (P < 0.05 between 10 mg/kg of FK888 and vehicle). The capsaicin desensitization, but not phosphoramidon, significantly reduced the UNDW-induced increase in Pao.

CONCLUSION

These results suggest that tachykinins, at least substance P, are involved in a part of the UNDW-induced bronchoconstriction in our guinea-pig model.

背景

吸入超声雾化蒸馏水（UNDW）仅在哮喘患者中诱发支气管收缩，但其反应的潜在机制尚未完全明确。我们最近发现，在被动致敏的豚鼠中，雾化抗原激发20分钟后吸入UNDW，支气管收缩会立即发生。

目的

本研究旨在探讨速激肽在该反应中的作用。

方法

将被动致敏的动物麻醉并进行人工通气，测量气道开口处压力（Pao）的变化，作为气道狭窄的总体指标。在抗原激发后15分钟静脉注射速激肽NK1和NK2双受体拮抗剂FK224以及速激肽NK1选择性拮抗剂FK888。还研究了辣椒素脱敏和中性内肽酶抑制剂磷酰胺素的作用。

结果

FK224和FK888均以剂量依赖性方式显著（分别为P < 0.05和P < 0.05）降低了UNDW吸入引起的Pao增加的时间进程曲线。吸入UNDW后1分钟时，与10 mg/kg FK224、1.0 mg/kg FK224和溶剂相比，Pao相对于抗原激发前值的增加百分比分别为267.4±17.1%、358.0±33.7%和412.4±27.6%（10 mg/kg FK224与溶剂之间P<0.01）；与10 mg/kg FK888、1.0 mg/kg FK888和溶剂相比，该值分别为254.4±48.5%、327.1±57.6%和418.5±39.0%（10 mg/kg FK888与溶剂之间P < 0.05）。辣椒素脱敏而非磷酰胺素显著降低了UNDW诱导的Pao增加。