Salmon J A, Tilling L C, Moncada S
Prostaglandins. 1985 Mar;29(3):377-85. doi: 10.1016/0090-6980(85)90097-8.
The effect on arachidonate metabolism of two compounds (BW755C and benoxaprofen) which have been reported to inhibit 5' lipoxygenase in leukocytes has been evaluated in human polymorphonuclear leukocytes (PMN) stimulated with the calcium ionophore A23187 and serum-treated zymosan (STZ). The syntheses of leukotriene B4 (LTB4) and thromboxane B2 (TXB2) from endogenous substrate were determined by specific radioimmunoassays as indicators of 5' lipoxygenase and cyclo-oxygenase activity in the PMN respectively. Benoxaprofen inhibited the synthesis of leukotriene B4 by human PMN stimulated with the calcium ionophore A23187, but it was approximately 5 times less potent than BW755C. However, benoxaprofen (IC50 1.6 X 10(-4)M) was approximately 100 times less potent than BW755C (IC50 1.7 X 10(-6)M) at inhibiting leukotriene B4 synthesis induced by serum-treated zymosan. Both drugs inhibited thromboxane synthesis by leukocytes stimulated with A23187 or serum-treated zymosan at similar concentrations (approximately 5 X 10(-6)M). The data obtained using STZ as stimulus are consistent with previous in vivo studies and indicate that benoxaprofen is a relatively selective inhibitor of cyclo-oxygenase. However, this selectivity was far less apparent when A23187 was used as a stimulus to release the eicosanoids which suggests that this inhibition could be via an indirect mechanism and therefore A23187 should be used with caution as a stimulus of 5' lipoxygenase for evaluating inhibitors of eicosanoid synthesis.
据报道，两种化合物（BW755C和苯恶洛芬）可抑制白细胞中的5'脂氧合酶，本研究在钙离子载体A23187和血清处理的酵母聚糖（STZ）刺激的人多形核白细胞（PMN）中评估了它们对花生四烯酸代谢的影响。通过特异性放射免疫测定法测定内源性底物合成白三烯B4（LTB4）和血栓素B2（TXB2）的情况，分别作为PMN中5'脂氧合酶和环氧化酶活性的指标。苯恶洛芬可抑制钙离子载体A23187刺激的人PMN合成白三烯B4，但其效力约为BW755C的五分之一。然而，在抑制血清处理的酵母聚糖诱导的白三烯B4合成方面，苯恶洛芬（IC50 1.6×10⁻⁴M）的效力约比BW755C（IC50 1.7×10⁻⁶M）低100倍。两种药物在相似浓度（约5×10⁻⁶M）下均可抑制A23187或血清处理的酵母聚糖刺激的白细胞合成血栓素。使用STZ作为刺激物获得的数据与先前的体内研究一致，表明苯恶洛芬是一种相对选择性的环氧化酶抑制剂。然而，当使用A23187作为刺激物释放类花生酸时，这种选择性就不那么明显了，这表明这种抑制可能是通过间接机制实现的，因此在评估类花生酸合成抑制剂时，应谨慎使用A23187作为5'脂氧合酶的刺激物。
