Hardy C C, Robinson C, Tattersfield A E, Holgate S T
N Engl J Med. 1984 Jul 26;311(4):209-13. doi: 10.1056/NEJM198407263110401.
Although prostaglandin D2 is the most abundant prostanoid generated by human lung mast cells and causes bronchoconstriction in animals, its effects have not been studied in human beings. We have compared the effects of inhaled prostaglandin D2 and prostaglandin F2 alpha on specific airway conductance in seven normal subjects and seven patients with mild allergic asthma. In dose-response studies in normal subjects, prostaglandin D2 caused a significant (20 +/- 6 per cent) fall in specific airway conductance after the two highest concentrations (250 and 500 micrograms per milliliter), whereas prostaglandin F2 alpha had no effect. In the asthmatic subjects, both prostaglandin D2 and prostaglandin F2 alpha caused a dose-related fall in specific airway conductance, starting at the lowest concentration of 4 micrograms per milliliter. Prostaglandin D2 was 3.5 times more potent than prostaglandin F2 alpha. In a single-dose study of both drugs (250 micrograms per milliliter), a minor fall in specific airway conductance occurred with prostaglandin D2 in the normal subjects, and a larger fall occurred with both drugs in the asthmatic subjects. Maximum effects were seen at three minutes: there was a 75 +/- 5 per cent fall with prostaglandin D2 and a 33 +/- 8 per cent fall with prostaglandin F2 alpha. These results suggest that prostaglandin D2 may be involved in the pathogenesis of bronchoconstriction in allergic asthma.
虽然前列腺素D2是人类肺肥大细胞产生的最丰富的前列腺素,且在动物中可引起支气管收缩,但其在人类中的作用尚未得到研究。我们比较了吸入前列腺素D2和前列腺素F2α对7名正常受试者和7名轻度过敏性哮喘患者的特定气道传导率的影响。在对正常受试者的剂量反应研究中,前列腺素D2在最高的两个浓度(250和500微克/毫升)后导致特定气道传导率显著下降(20±6%),而前列腺素F2α没有影响。在哮喘患者中,前列腺素D2和前列腺素F2α均导致特定气道传导率呈剂量相关下降,从最低浓度4微克/毫升开始。前列腺素D2的效力是前列腺素F2α的3.5倍。在两种药物(250微克/毫升)的单剂量研究中,正常受试者吸入前列腺素D2后特定气道传导率有轻微下降,哮喘患者吸入两种药物后下降幅度更大。在三分钟时观察到最大效应:前列腺素D2导致下降75±5%,前列腺素F2α导致下降33±8%。这些结果表明,前列腺素D2可能参与过敏性哮喘中支气管收缩的发病机制。