Rajakulasingam K, Johnston S L, Ducey J, Ritter W, Howarth P H, Holgate S T
Department of Allergy and Immunology, National Heart and Lung Institute, London, United Kingdom.
J Appl Physiol (1985). 1996 Jun;80(6):1973-7. doi: 10.1152/jappl.1996.80.6.1973.
The role of the thromboxane A2 (TxA2) receptor in bradykinin-induced bronchial responses was investigated in this study by using a selective and potent TxA2-receptor antagonist BAY u 3405. Eleven asthmatic subjects were randomized to receive 50 mg of BAY u 3405 or matched placebo in a crossover and double-blind fashion. Ninety minutes after dosing, serum was taken for drug assay, and subjects underwent provocation with bradykinin or prostaglandin D2 (PGD2) to determine bronchial responsiveness [provocative concentration of agonist required to produce a 20% fall in forced expiratory volume in 1 s from the postdiluent baseline (PC20)]. Pretreatment with BAY u 3405 caused a twofold doubling-dilution reduction in bronchial reactivity to PGD2; the geometric mean PC20 values were 0.132 (0.015-0.871) and 0.034 (0.008-0.095) mg/ml, respectively, for active and placebo days (P = 0.001). There was, however, no significant difference in PC20 values for bradykinin between active and placebo treatment days. We have demonstrated that BAY u 3405 caused a significant inhibition of bronchconstriction induced by inhaled PGD2 but had no influence on bronchial responsiveness to inhaled bradykinin. This study suggests therefore that TxA2 receptors do not play a role in bradykinin-induced bronchoconstriction in asthma.
本研究通过使用一种选择性强效血栓素A2（TxA2）受体拮抗剂BAY u 3405，探讨了TxA2受体在缓激肽诱导的支气管反应中的作用。11名哮喘患者被随机分为两组，采用交叉双盲方式，分别接受50 mg的BAY u 3405或匹配的安慰剂。给药90分钟后，采集血清进行药物检测，然后让受试者接受缓激肽或前列腺素D2（PGD2）激发试验，以确定支气管反应性[从稀释后基线开始，使1秒用力呼气量下降20%所需的激动剂激发浓度（PC20）]。用BAY u 3405预处理后，对PGD2的支气管反应性降低了两倍稀释度；活性药物组和安慰剂组的几何平均PC20值分别为0.132（0.015 - 0.871）和0.034（0.008 - 0.095）mg/ml（P = 0.001）。然而，活性药物组和安慰剂治疗组之间缓激肽的PC20值没有显著差异。我们已经证明，BAY u 3405对吸入PGD2诱导的支气管收缩有显著抑制作用，但对吸入缓激肽的支气管反应性没有影响。因此，本研究表明TxA2受体在哮喘患者缓激肽诱导的支气管收缩中不起作用。
