Stahl G L, Tsao P, Lefer A M, Ramphal J Y, Nicolaou K C
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Eur J Pharmacol. 1989 Apr 12;163(1):55-60. doi: 10.1016/0014-2999(89)90394-4.
In this study, we have investigated the biological activities of LxA5 and LxB5 in isolated smooth muscle preparations of the guinea pig. LxA5 slowly contracted pulmonary parenchymal strips isolated from guinea pigs in a concentration-dependent manner over the range of 0.1-2.2 microM. This bronchoconstrictor effect was not associated with release of peptide leukotrienes (i.e. LTC4, LTD4 and LTE4) and only a slight increase in thromboxane B2. Furthermore, the bronchoconstrictor effect was not blocked by lipoxygenase inhibitors, suggesting the pulmonary effect is not mediated by lipoxygenase products. However, a peptide leukotriene receptor antagonist (e.g. SK&F-104353) inhibited or reversed the LxA5 response indicating that LxA5 and the peptide leukotrienes may share the same receptor. In contrast to LxA5, LxB5 displayed no significant bronchoconstrictor effect at concentrations up to 2.2 microM. Moreover, LxA5 and LxB5 did not exert a significant endothelium-dependent vasorelaxation in aortic vascular smooth muscle as do LxA4 and LxB4. Thus, LxA5 and LxB5 display a unique biological profile which differs from LxA4 and LxB4. LxA4 may be a mediator in circulatory disease states (e.g. myocardial ischemia, circulatory shock), but LxA5 and LxB5 are not as likely candidates as mediators of disease.
在本研究中，我们研究了LxA5和LxB5在豚鼠离体平滑肌制剂中的生物活性。LxA5在0.1 - 2.2微摩尔的浓度范围内，以浓度依赖性方式缓慢收缩从豚鼠分离的肺实质条带。这种支气管收缩作用与肽白三烯（即LTC4、LTD4和LTE4）的释放无关，且血栓素B2仅略有增加。此外，脂氧合酶抑制剂不能阻断支气管收缩作用，这表明肺部效应不是由脂氧合酶产物介导的。然而，一种肽白三烯受体拮抗剂（如SK&F - 104353）可抑制或逆转LxA5反应，这表明LxA5和肽白三烯可能共用相同的受体。与LxA5相反，LxB5在浓度高达2.2微摩尔时未显示出明显的支气管收缩作用。此外，LxA5和LxB5不像LxA4和LxB4那样在主动脉血管平滑肌中产生显著的内皮依赖性血管舒张作用。因此，LxA5和LxB5表现出与LxA4和LxB4不同的独特生物学特性。LxA4可能是循环系统疾病状态（如心肌缺血、循环性休克）的介质，但LxA5和LxB5作为疾病介质的可能性较小。
