Lawson C, Bunting S, Holzgrefe H, Fitzpatrick F
J Pharmacol Exp Ther. 1986 Jun;237(3):888-92.
In contrast to its established myotropic effect on guinea-pig lung parenchyma, the myotropic action of leukotriene B4 on the trachea is uncertain. Our characterization of its effects on the latter organ indicates that leukotriene B4 contracts guinea-pig trachea zig-zag strips in a concentration-dependent manner from 5 X 10(-9) to 5 X 10(-7) M. Leukotriene B4 was at least 10 times more potent than histamine, but 10 times less potent than leukotriene C4. Similar effects were evident with 20-hydroxyleukotriene B4; however, this metabolite contracted the trachea less forcefully. Tracheas developed tachyphylaxis after cumulative administration of leukotriene B4, but not 20-hydroxyleukotriene B4. The myotropic effect of leukotriene B4 was attributable to an indirect mechanism involving formation of cyclooxygenase metabolites of arachidonic acid. For example, the levels of prostaglandin E2 and prostaglandin F2 alpha released into the incubation medium correlated with the contractile response, and suppression of their biosynthesis with cyclooxygenase inhibitors eliminated that response. We conclude that myotropic effects of leukotriene B4 occur in central airways in addition to peripheral airways. The contribution of leukotriene B4 to tracheal bronchospasm is not necessarily negligible.
与白三烯B4对豚鼠肺实质已确定的亲肌作用相反，其对气管的亲肌作用尚不确定。我们对其对气管的作用特性进行的研究表明，白三烯B4在5×10⁻⁹至5×10⁻⁷M浓度范围内以浓度依赖的方式使豚鼠气管之字形条带收缩。白三烯B4的效力至少比组胺强10倍，但比白三烯C4弱10倍。20-羟基白三烯B4也有类似作用；然而，这种代谢产物使气管收缩的力度较小。在累积给予白三烯B4后气管出现快速耐受性，但给予20-羟基白三烯B4后未出现。白三烯B4的亲肌作用归因于一种间接机制，该机制涉及花生四烯酸环氧化酶代谢产物的形成。例如，释放到孵育培养基中的前列腺素E2和前列腺素F2α水平与收缩反应相关，用环氧化酶抑制剂抑制其生物合成可消除该反应。我们得出结论，白三烯B4的亲肌作用除了在外周气道发生外，在中央气道也会出现。白三烯B4对气管支气管痉挛的作用不一定可忽略不计。
