Silbaugh S A, Stengel P W, Pechous P A, Marshall W S
Department of Immunology, Pulmonary and Leukotriene Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
Am Rev Respir Dis. 1989 Sep;140(3):610-4. doi: 10.1164/ajrccm/140.3.610.
Conscious Hartley guinea pigs were challenged with LTD4 or LTE4 aerosols. When dynamic compliance (Cdyn) decreased to 50% of its baseline value, the challenge aerosols were stopped and treatment aerosols of salbutamol, the LTD4/E4 antagonist LY171883 Na, atropine, or sodium chloride (control) were begun. After 5 min of continuous exposure to the treatment aerosol, each animal was killed and excised lung gas volume (ELGV) was measured. Salbutamol was equally effective in reversing LTD4- and LTE4-induced Cdyn changes. Aerosolized LY171883 Na was effective against both agonists, but was about threefold more potent against LTE4. In contrast, atropine was very effective in reversing LTD4-induced Cdyn changes, but produced minimal reversal when LTE4 was the challenge agent. Pulmonary gas trapping results supported these observations; ELGV values were closely correlated with 5-min Cdyn measurements for both LTD4 (r = -0.817) and LTE4 (r = -0.831). Thus, although LTD4 and LTE4 are though to act on the same or similar receptors, the pattern of pharmacologic reversal at comparable levels of airway obstruction differs for these two agonists.
清醒的哈特利豚鼠接受LTD4或LTE4气雾剂刺激。当动态顺应性（Cdyn）降至其基线值的50%时，停止刺激气雾剂，并开始给予沙丁胺醇、LTD4/E4拮抗剂LY171883 Na、阿托品或氯化钠（对照）的治疗气雾剂。连续暴露于治疗气雾剂5分钟后，处死每只动物并测量切除的肺气体容积（ELGV）。沙丁胺醇在逆转LTD4和LTE4诱导的Cdyn变化方面同样有效。雾化的LY171883 Na对两种激动剂均有效，但对LTE4的效力约为其三倍。相比之下，阿托品在逆转LTD4诱导的Cdyn变化方面非常有效，但当LTE4为刺激剂时，其逆转作用最小。肺气体潴留结果支持了这些观察结果；LTD4（r = -0.817）和LTE4（r = -0.831）的ELGV值与5分钟Cdyn测量值密切相关。因此，尽管LTD4和LTE4被认为作用于相同或相似的受体，但在气道阻塞程度相当的情况下，这两种激动剂的药理学逆转模式不同。
