Ueno A, Tokumasu T, Naraba H, Oh-ishi S
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Jpn J Pharmacol. 1996 Apr;70(4):285-90. doi: 10.1254/jjp.70.285.
The injection of lipopolysaccharide (LPS) from E. Coli into the dorsal skin of rats caused a dose-dependent increase in vascular permeability as measured by the extravasation over a 40-min period of intravenously injected dye. This increase caused by LPS was attenuated by pretreatment with the bradykinin (BK) receptor antagonist HOE140, the selective platelet-activating factor (PAF) antagonist TCV309, and by combined treatment with mepyramine and methysergide. Combined treatment with HOE140 and TCV309 resulted in further suppression than that achieved with a single treatment alone. By the simultaneous pretreatment with all antagonists, the response was almost totally abolished. On the other hand, indomethacin also inhibited the response induced by LPS, but not those induced by BK and PAF itself. A small dose of BK or histamine synergistically potentiated the effect of PAF when simultaneously injected. These results suggest that BK, PAF, histamine/serotonin and prostaglandins are involved in the LPS-induced increase in vascular permeability, where PAF, in addition to its direct action, potentiates the response to BK and histamine, and prostaglandins potentiate the actions of other mediators without its direct action.
将大肠杆菌的脂多糖（LPS）注射到大鼠背部皮肤，通过静脉注射染料在40分钟内的渗出量来测量，结果显示血管通透性呈剂量依赖性增加。LPS引起的这种增加可被缓激肽（BK）受体拮抗剂HOE140、选择性血小板活化因子（PAF）拮抗剂TCV309预处理以及与美吡拉敏和甲基麦角新碱联合治疗所减弱。HOE140和TCV309联合治疗比单独使用单一治疗产生的抑制作用更强。通过同时用所有拮抗剂进行预处理，反应几乎完全被消除。另一方面，吲哚美辛也抑制LPS诱导的反应，但不抑制BK和PAF本身诱导的反应。小剂量的BK或组胺在同时注射时可协同增强PAF的作用。这些结果表明，BK、PAF、组胺/5-羟色胺和前列腺素参与了LPS诱导的血管通透性增加，其中PAF除了其直接作用外，还增强了对BK和组胺的反应，而前列腺素在无直接作用的情况下增强了其他介质的作用。
