Inhibition of the neutrophil oxidative burst and degranulation by phenothiazines.
Inhibition of the neutrophil oxidative burst and degranulation by phenothiazines.
复制标题
吩噻嗪抑制中性粒细胞氧化爆发和脱粒。
DOI：
10.1016/0006-291x(81)91631-4
复制
发表时间：
1981
影响因子：
3.1
通讯作者：
Reed,PW
中科院分区：
文献类型：
--
作者：
Ochs,DL;Reed,PW
三氟拉嗪抑制花生四烯酸、N-甲酰甲硫氨酰苯丙氨酸、毛地黄皂苷或离子载体A23187孵育的豚鼠中性粒细胞产生超氧阴离子和摄取氧，IC_（50）值为7- 37 μ M。由于这种抑制作用是由抑制钙调蛋白与蛋白质相互作用的三氟拉嗪浓度产生的，我们研究了其他两种与钙调蛋白相互作用不太有效的吩噻嗪的影响。氯丙嗪、异丙嗪和三氟拉嗪都以相似的效率抑制N-甲酰甲硫氨酰苯丙氨酸刺激的超氧化物产生。此外，A23187或N-甲酰甲硫氨酰苯丙氨酸刺激的脱粒被所有三种吩噻嗪类似地抑制，IC 50值为18-45 μ M。这些结果与吩噻嗪类药物可能通过与细胞膜的非特异性相互作用而不是通过与钙调蛋白的特异性相互作用来抑制中性粒细胞功能的观点一致。
Trifluoperazine inhibits superoxide production and O2uptake by guinea pig neutrophils incubated with arachidonic acid, N-formylmethionylphenylalanine, digitonin or ionophore A23187, with IC50values of 7–37uM. Since this inhibition is produced by concentrations of trifluoperazine which inhibit interaction of calmodulin with proteins, we examined the effects of two other phenothiazines which interact less effectively with calmodulin. Chlorpromazine, promethazine and trifluoperazine all inhibit N-formylmethionylphenylalanine-stimulated superoxide production with similar efficiency. Furthermore, degranulation stimulated by A23187 or N-formylmethionylphenylalanine is inhibited similarly by all three phenothiazines with IC50values of 18–45 uM. These results are consistent with the suggestion that phenothiazines may inhibit neutrophil function as a result of non-specific interactions with the cells' membranes rather than by specific interaction with calmodulin.