Chlorpromazine inhibits neutrophil chemotaxis beyond the chemotactic receptor-ligand interaction.
Chlorpromazine inhibits neutrophil chemotaxis beyond the chemotactic receptor-ligand interaction.
复制标题
氯丙嗪抑制中性粒细胞的趋化性超出趋化受体-配体相互作用。
DOI：
10.1093/infdis/150.5.643
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
C. Kurth
中科院分区：
文献类型：
--
作者：
K. Lohr;J. Feix;C. Kurth
吩噻嗪可能通过与钙调蛋白结合或通过疏水相互作用扰乱膜结构来抑制 Ca++ 依赖性中性粒细胞功能。我们研究了氯丙嗪 (CPZ) 对人多形核中性粒细胞 (PMN) 趋化寡肽受体和 PMN 膜流动性的影响。 CPZ 对 Boyden 室中的 PMN 运动具有可逆的双相作用（5 µM 时轻微抑制，10 µM 时增强，较高浓度时呈剂量依赖性抑制）。抑制运动的效力顺序（三氟拉嗪大于 CPZ 大于异丙嗪）与抑制超氧化物 (O-2) 释放和与钙调蛋白结合的抑制顺序相同。 CPZ 非特异性改变趋化性 fMet-Leu-[3H]Phe 的结合亲和力。通过两个自旋探针进行评估，在抑制 PMN 受体介导的趋化性和 O-2 释放的 CPZ 浓度下，PMN 膜的流动性没有改变。数据表明，CPZ 非特异性地改变受体亲和力并独立抑制趋化性和 O-2 释放，而不改变整体膜的流动性。我们推测，测试功能的常见易位步骤中未识别的“受体后变化”解释了观察到的抑制。
Phenothiazines depress Ca++-dependent neutrophil functions, perhaps by binding to calmodulin or perturbing membrane structure through hydrophobic interactions. We examined effects of chlorpromazine (CPZ) on the human polymorphonuclear neutrophil (PMN) chemotactic-oligopeptide receptor and PMN membrane fluidity. CPZ had a reversible, biphasic effect on PMN motility in the Boyden chamber (slight depression at 5 microM, enhancement at 10 microM, and dose-dependent inhibition at higher concentrations). Order of potency for inhibition of motility (trifluoperazine greater than CPZ greater than promethazine) was identical to that for both inhibition of superoxide (O-2) release and binding to calmodulin. CPZ nonspecifically altered the binding affinity of chemotactic fMet-Leu-[3H]Phe. As assessed with two spin-probes, PMN membrane fluidity was unaltered at CPZ concentrations that depressed PMN receptor-mediated chemotaxis and O-2 release. The data suggest that CPZ nonspecifically alters receptor affinity and depresses chemotaxis and O-2 release independently, without altering bulk membrane fluidity. We speculate that unidentified "post-receptor changes" at a common translocation step for functions tested account for the observed inhibition.