白三烯B4、C4和D4对豚鼠肺组织花生四烯酸代谢的刺激作用及体外血栓素A2的生成
Stimulation of arachidonic acid metabolism and generation of thromboxane A2 by leukotrienes B4, C4 and D4 in guinea-pig lung in vitro.
作者信息
Piper P J, Samhoun M N
出版信息
Br J Pharmacol. 1982 Oct;77(2):267-75. doi: 10.1111/j.1476-5381.1982.tb09295.x.
1 Leukotriene C4 (LTC4), LTD4, slow-reacting substance of anaphylaxis (SRS-A) (from guinea-pig lung), bradykinin (Bk) and arachidonic acid (AA) release thromboxane A2 (TxA2) and prostaglandin-like materials from guinea-pig isolated perfused lungs. 2 Release of TxA2 induced by LTC4 and LTD4 is inhibited by a thromboxane synthetase inhibitor, imidazole (2.9 mM). 3 Mepacrine (200 microM), a phospholipase inhibitor, inhibits release of TxA2 and prostaglandin-like materials caused by SRS-A and Bk but not that due to exogenous AA 4 Leukotrienes B4, C4 and D4 are approximately equipotent in inducing dose-related contractions of guinea-pig parenchymal strips (GPPs). 5 Leukotriene-induced contractions of GPPs are greatly inhibited by imidazole (2.9 mM), carboxyheptylimidazole (24 microM) and mepacrine (400 microM). 6 FPL 55712 (1.9 microM), the SRS-A antagonist, blocks contractions of GPPs induced by LTC4 and LTD4 but not those due to LTB4 or Bk. 7 Tachyphylaxis to LTB4 occurs in GPPs but not to LTC4 or LTD4. 8 These results suggest that in guinea-pig lung in vitro, LTB4, LTC4 and LTD4 activate a phospholipase with subsequent generation of cyclo-oxygenase products of which TxA2 plays an important role.
1 白三烯C4（LTC4）、白三烯D4（LTD4）、过敏反应慢反应物质（SRS - A，来自豚鼠肺）、缓激肽（Bk）和花生四烯酸（AA）可使豚鼠离体灌注肺释放血栓素A2（TxA2）和前列腺素样物质。2 血栓素合成酶抑制剂咪唑（2.9 mM）可抑制LTC4和LTD4诱导的TxA2释放。3 磷脂酶抑制剂米帕林（200 microM）可抑制SRS - A和Bk引起的TxA2和前列腺素样物质的释放，但不抑制外源性AA引起的释放。4 白三烯B4、C4和D4在诱导豚鼠实质条（GPPs）剂量相关的收缩方面大致等效。5 咪唑（2.9 mM）、羧基庚基咪唑（24 microM）和米帕林（400 microM）可显著抑制白三烯诱导的GPPs收缩。6 SRS - A拮抗剂FPL 55712（1.9 microM）可阻断LTC4和LTD4诱导的GPPs收缩，但不阻断LTB4或Bk引起的收缩。7 GPPs对LTB4会产生快速耐受性，但对LTC4或LTD4不会。8 这些结果表明，在体外豚鼠肺中，LTB4、LTC4和LTD4激活磷脂酶，随后生成环氧化酶产物，其中TxA2起重要作用。
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