Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs
Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs
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DOI：
10.1016/j.pupt.2006.05.004
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发表时间：
2007-01-01
影响因子：
3.2
通讯作者：
Liu, Qi
中科院分区：
文献类型：
--
作者：
Fujimura, Masaki;Liu, Qi
研究了选择性磷酸二酯酶3(PDE3)抑制剂奥普利酮和选择性PDE4抑制剂SB207499对抗原诱导的豚鼠咳嗽反射敏感性增加和对辣椒素正常咳嗽反应的影响。主动致敏豚鼠吸入辣椒素(10(-8)、10(-6)和10(-4)M)后24 h计数咳嗽次数，然后进行支气管肺泡灌洗(BAL)。奥普利酮(1或10 mg/kg)或SB207499(1或10 mg/kg)分别于抗原激发后1h和辣椒素激发前1h两次给药。SB207499显著降低抗原诱导的致敏动物吸入辣椒素引起的咳嗽反应，而非致敏动物的正常咳嗽反应显著降低，但不是奥普利酮。S13207499也能降低抗原诱导的BAL嗜酸性粒细胞增多率，但奥普利酮不能。PDE4抑制剂可能通过抑制过敏性呼吸道炎症和咳嗽反射的常见途径而有效地治疗与呼吸道过敏相关的咳嗽。(C)2006爱思唯尔有限公司。保留所有权利。
Effects of the selective phosphodiesterase 3 (PDE3) inhibitor olprinone and the selective PDE4 inhibitor SB207499 were investigated on antigen-induced increase of cough reflex sensitivity and normal Cough response to capsaicin in guinea pigs. Number of coughs elicited by inhalation of capsaicin (10(-8), 10(-6) and 10(-4) M) Was counted 24 h after an antigen challenge in actively sensitized guinea pigs, and then bronchoalveolar lavage (BAL) was performed. Olprinone (1 or 10 mg/kg) or SB207499 (1 or 10 mg/kg) was given twice intraperitoneally: One hour after the antigen challenge and 1 h before the capsaicin provocation. SB207499, but not olprinone, significantly reduced both antigen-induced increase of cough response to inhaled capsaicin in sensitized animals and normal cough response in non-sensitized animals. S13207499, but not olprinone, also reduced the antigen-induced BAL eosinophilia. PDE4 inhibitors may be useful in treating cough associated With airway allergy via inhibiting both allergic airway inflammation and the common pathway of cough reflex. (c) 2006 Elsevier Ltd. All rights reserved.