Sampson S E, Sampson A P, Costello J F
Department of Respiratory Medicine, King's College School of Medicine and Dentistry, London, UK.
Thorax. 1997 Jun;52(6):513-8. doi: 10.1136/thx.52.6.513.
Prostaglandin (PG) D2 is a potent bronchoconstrictor mediator and is found, together with leukotriene (LT) D4, in bronchoalveolar lavage fluid during the early response to allergen challenge in asthmatic subjects. The potency of PGD2 has not been established in normal and atopic non-asthmatic subjects, nor has the contribution of cholinergic mechanisms to PGD2 induced bronchoconstriction in normal subjects. Mediators released simultaneously may interact, so the effect of pre-inhalation of LTD4 on PGD2 responsiveness was investigated.
Six normal and six atopic non-asthmatic subjects performed histamine and PGD2 challenges on separate occasions. Eight normal subjects performed PGD2 challenges immediately before and 45 minutes after inhalation of 200 micrograms oxitropium bromide or placebo. Bronchial responsiveness to PGD2 was established in six normal subjects immediately after pretreatment with saline or non-bronchoconstricting doses of methacholine or LTD4 (challenge 1), and again at six hours (challenge 2). All studies were performed in a double blind, randomised, crossover fashion.
PGD2 was 25-fold and 18-fold more potent as a bronchoconstrictor than histamine in atopic non-asthmatic and normal subjects, respectively. Responsiveness (PC35sGaw) to histamine and PGD2 correlated significantly (r = 0.917, n = 12, p < 0.001). Oxitropium bromide in a dose of 200 micrograms inhibited PGD2 induced bronchoconstriction by 37.5%, although in two of these subjects no inhibition was seen. Pre-inhalation of LTD4 and methacholine shifted the dose-response curve of PGD2 to the left by 4.6-fold and 2.4-fold, respectively.
PGD2 is a potent bronchoconstrictor in normal subjects, which is partly mediated by cholinergic mechanisms in some subjects. No significant interaction was found between LTD4 and PGD2 in six normal subjects.
前列腺素（PG）D2是一种强效支气管收缩介质，在哮喘患者过敏原激发早期反应期间，它与白三烯（LT）D4一起存在于支气管肺泡灌洗液中。PGD2在正常和特应性非哮喘受试者中的效力尚未确定，胆碱能机制对正常受试者中PGD2诱导的支气管收缩的作用也未明确。同时释放的介质可能相互作用，因此研究了预先吸入LTD4对PGD2反应性的影响。
6名正常受试者和6名特应性非哮喘受试者分别进行组胺和PGD2激发试验。8名正常受试者在吸入200微克氧托溴铵或安慰剂之前和之后45分钟进行PGD2激发试验。在6名正常受试者中，用生理盐水或无支气管收缩作用剂量的乙酰甲胆碱或LTD4预处理后立即（激发试验1）以及6小时后（激发试验2）确定对PGD2的支气管反应性。所有研究均采用双盲、随机、交叉方式进行。
在特应性非哮喘和正常受试者中，PGD2作为支气管收缩剂的效力分别比组胺高25倍和18倍。对组胺和PGD2的反应性（PC35sGaw）显著相关（r = 0.917，n = 12，p < 0.001）。200微克剂量的氧托溴铵可抑制PGD2诱导的支气管收缩37.5%，尽管其中2名受试者未观察到抑制作用。预先吸入LTD4和乙酰甲胆碱分别使PGD2的剂量反应曲线向左移动4.6倍和2.4倍。
PGD2在正常受试者中是一种强效支气管收缩剂，在某些受试者中部分由胆碱能机制介导。在6名正常受试者中未发现LTD4与PGD2之间有显著相互作用。
