Lohr K M, Feix J B, Kurth C
J Infect Dis. 1984 Nov;150(5):643-52. doi: 10.1093/infdis/150.5.643.
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.
吩噻嗪类药物可抑制依赖钙离子的中性粒细胞功能，可能是通过与钙调蛋白结合或通过疏水相互作用扰乱膜结构来实现的。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对博伊登小室中PMN的运动具有可逆的双相作用（5微摩尔时轻度抑制，10微摩尔时增强，更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顺序相同。CPZ非特异性地改变了趋化性fMet-Leu-[3H]Phe的结合亲和力。用两种自旋探针评估，在降低PMN受体介导的趋化性和O-2释放的CPZ浓度下，PMN膜流动性未改变。数据表明，CPZ非特异性地改变受体亲和力，并独立地抑制趋化性和O-2释放，而不改变膜的整体流动性。我们推测，在测试功能的共同易位步骤中，未确定的“受体后变化”是观察到的抑制作用的原因。
