Blackwood R A, Hessler R J
Department of Pediatrics, University of Michigan Medical Center, Ann Arbor 48109-0244, USA.
J Leukoc Biol. 1995 Jul;58(1):114-8. doi: 10.1002/jlb.58.1.114.
The phenothiazines are known to be potent inhibitors of calmodulin and have been used as probes for examining calmodulin-dependent cellular functions. We report here that the characteristics of phenothiazine inhibition of exocytosis in neutrophils more closely resemble their interaction with the annexins in vitro. Ca(2+)-dependent aggregation of liposomes mediated by either annexin I or annexin II was inhibited by the phenothiazines. Inhibition of liposome aggregation was not caused by interference with the binding of annexins to phospholipids. Rather, the phenothiazines increased the concentration of Ca2+ required for aggregation. Likewise, in neutrophils permeabilized with streptolysin O, inhibition of degranulation by phenothiazines could be overcome by increasing [Ca2+]. These results suggest that inhibition by phenothiazines of neutrophil degranulation is secondary to the ability of these compounds to inhibit membrane-membrane contact promoted by the annexins.
已知吩噻嗪类药物是钙调蛋白的强效抑制剂，并已被用作研究钙调蛋白依赖性细胞功能的探针。我们在此报告，吩噻嗪类药物对中性粒细胞胞吐作用的抑制特性更类似于它们在体外与膜联蛋白的相互作用。吩噻嗪类药物可抑制由膜联蛋白I或膜联蛋白II介导的脂质体的Ca(2+)依赖性聚集。脂质体聚集的抑制并非由干扰膜联蛋白与磷脂的结合所致。相反，吩噻嗪类药物增加了聚集所需的Ca2+浓度。同样，在用链球菌溶血素O通透的中性粒细胞中，增加[Ca2+]可克服吩噻嗪类药物对脱颗粒作用的抑制。这些结果表明，吩噻嗪类药物对中性粒细胞脱颗粒作用的抑制是这些化合物抑制膜联蛋白促进的膜-膜接触能力的继发效应。
