Snyder D W, Krell R D
Prostaglandins. 1986 Aug;32(2):189-200. doi: 10.1016/0090-6980(86)90124-3.
The contractile activities of peptide leukotrienes (LT) on isolated spiral strips of ferret trachea were characterized pharmacologically. LTC4 and LTD4 contracted ferret tracheal strips in a concentration-related manner and were 3- to 8-fold more potent than carbachol. In contrast, high concentrations of LTE4 evoked either weak contractions or none at all, whereas LTC4 and D4 were partial agonists compared to carbachol. In tissues which were unresponsive to LTE4, this compound antagonized contractile responses to LTC4 and D4 in an apparently competitive manner: Carbachol-induced contractions were not altered by LTE4. The cyclooxygenase inhibitor, indomethacin (5 microM), LT antagonist, FPL55712 (10 microM), atropine (1 microM), phenoxybenzamine (10 microM), and LTB4 (10 microM) failed to alter LTC4 and D4 concentration-response curves. The results indicate that ferret trachea is sensitive to the contractile activity of LTC4 and LTD4 but not LTE4. The LT-induced contractions appear to be mediated by a direct action of the LT rather than indirectly through release of secondary mediators such as thromboxane, prostaglandin, or acetylcholine. LT receptors in ferret trachea are insensitive to FPL55712 but are antagonized by LTE4.
对雪貂气管分离螺旋条上肽白三烯（LT）的收缩活性进行了药理学特征分析。LTC4和LTD4以浓度相关的方式使雪貂气管条收缩，其效力比卡巴胆碱强3至8倍。相比之下，高浓度的LTE4要么引起微弱收缩，要么根本不引起收缩，而与卡巴胆碱相比，LTC4和D4是部分激动剂。在对LTE4无反应的组织中，该化合物以明显竞争性的方式拮抗对LTC4和D4的收缩反应：LTE4不改变卡巴胆碱诱导的收缩。环氧合酶抑制剂吲哚美辛（5微摩尔）、LT拮抗剂FPL55712（10微摩尔）、阿托品（1微摩尔）、酚苄明（10微摩尔）和LTB4（10微摩尔）未能改变LTC4和D4的浓度-反应曲线。结果表明，雪貂气管对LTC4和LTD4的收缩活性敏感，但对LTE4不敏感。LT诱导的收缩似乎是由LT的直接作用介导的，而不是通过释放血栓素、前列腺素或乙酰胆碱等二级介质间接介导的。雪貂气管中的LT受体对FPL55712不敏感，但可被LTE4拮抗。
