Heller R S, Herman R P, Herman C A
Department of Biology, New Mexico State University, Las Cruces 88003.
Can J Physiol Pharmacol. 1989 Apr;67(4):309-14. doi: 10.1139/y89-050.
Leukotrienes (LTs) have been shown to cause contraction of mammalian airway smooth muscle. In this study, LTC4, LTD4, and LTE4 were tested on isolated strips of bullfrog lung. LTC4, LTD4, and LTE4 (10(-7) to 3 x 10(-10) M) stimulated lung contraction. LTC4 was the most potent, with LTD4 and LTE4 being of equal but lower potency. The cyclooxygenase inhibitors, indomethacin and ibuprofen, had no effect on the strength of leukotriene-induced contraction. In addition, the effects of three mammalian LTD4 receptor antagonists, L-649,923, L-648,051, and LY171883 were tested. All three antagonists failed to block LTC4-simulated contraction, but were effective blockers of LTD4. LTE4-stimulated contractions were significantly blunted by all three antagonists, but the extent of blockade was less than for LTD4. Significant bioconversion of [3H]LTC4 to LTD4 and LTE4 occurred in minced lung preparations but not in lung strips. Peptide leukotrienes caused contraction in amphibian lung, though the order of potency differs from mammals. Like mammals, frogs appear to have two classes of leukotriene receptors, one for LTC4 and one for LTD4-LTE4. These results support the hypothesis that leukotriene receptors have been highly conserved through evolution, despite the fact that the nature of tissue responsiveness to leukotrienes has changed over evolutionary time.
白三烯（LTs）已被证明可引起哺乳动物气道平滑肌收缩。在本研究中，对牛蛙肺的离体组织条进行了LTC4、LTD4和LTE4的测试。LTC4、LTD4和LTE4（10^(-7)至3×10^(-10) M）可刺激肺收缩。LTC4的作用最强，LTD4和LTE4的作用强度相当但较弱。环氧化酶抑制剂吲哚美辛和布洛芬对白三烯诱导的收缩强度没有影响。此外，还测试了三种哺乳动物LTD4受体拮抗剂L-649,923、L-648,051和LY171883的作用。所有三种拮抗剂均未能阻断LTC4刺激的收缩，但对LTD4有效。所有三种拮抗剂均使LTE4刺激的收缩明显减弱，但阻断程度小于LTD4。在切碎的肺组织中发生了[3H]LTC4向LTD4和LTE4的显著生物转化，但在肺组织条中未发生。肽白三烯可引起两栖动物肺收缩，尽管其效力顺序与哺乳动物不同。与哺乳动物一样，青蛙似乎有两类白三烯受体，一类针对LTC4，另一类针对LTD4-LTE4。这些结果支持这样的假设，即尽管随着进化时间的推移，组织对白三烯的反应性质发生了变化，但白三烯受体在进化过程中一直高度保守。
