Wang J P, Hsu M F, Kuo S C
Department of Medical Research, Taichung Veterans General Hospital, Taiwan, ROC.
Eur J Pharmacol. 1997 Jan 14;319(1):131-6. doi: 10.1016/s0014-2999(96)00836-9.
In rat neutrophils, formyl-Met-Leu-Phe (fMLP)-induced phosphate formation was inhibited by abruquinone A (IC50 value about 32.7 +/- 6.4 microM) as well as by a putative phospholipase C inhibitor, [6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole- 2,5-dione (U73122) (IC50 value about 11.3 +/- 1.2 microM). The reduction in inositol phosphate levels appeared to reflect inhibition of phospholipase C activity because the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) catalyzed by a soluble fraction from neutrophils was also inhibited by abruquinone A (IC50 value about 31.4 +/- 5.6 microM) over the same range of concentrations. Although abruquinone A alone induced Ca2+ and Mn2+ influx into neutrophils in Ca(2+)-containing medium, abruquinone A, like U73122, inhibited Ca2+ release (IC50 value about 23.5 +/- 0.5 microM) from internal stores in Ca(2+)-free medium. These results indicate that abruquinone A inhibits the activity of phosphoinositide-specific phospholipase C in neutrophils.
在大鼠中性粒细胞中，阿布鲁醌A（IC50值约为32.7±6.4微摩尔）以及一种假定的磷脂酶C抑制剂[6-[[17β-3-甲氧基雌甾-1,3,5(10)-三烯-17-基]氨基]己基]-1H-吡咯-2,5-二酮（U73122）（IC50值约为11.3±1.2微摩尔）可抑制甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）诱导的磷酸盐生成。肌醇磷酸水平的降低似乎反映了磷脂酶C活性的抑制，因为在相同浓度范围内，中性粒细胞可溶部分催化的磷脂酰肌醇4,5-二磷酸（PIP2）水解也受到阿布鲁醌A（IC50值约为31.4±5.6微摩尔）的抑制。尽管单独的阿布鲁醌A在含钙培养基中可诱导Ca2+和Mn2+流入中性粒细胞，但与U73122一样，阿布鲁醌A在无钙培养基中可抑制细胞内储存的Ca2+释放（IC50值约为23.5±0.5微摩尔）。这些结果表明，阿布鲁醌A可抑制中性粒细胞中磷酸肌醇特异性磷脂酶C的活性。
