Haggerty J G, Jackson R C
J Biol Chem. 1983 Feb 10;258(3):1819-25.
We have developed a rapid turbidimetric assay for the release of cortical granule contents from cortices prepared from eggs of the sea urchin, Strongylocentrotus purpuratus. The decrease in turbidity of cortex suspensions which occurs when the free calcium ion concentration is increased to 0.38-0.62 microM can be followed spectrophotometrically. Kinetic experiments demonstrate that this calcium-triggered turbidity change occurs rapidly and with no detectable lag period. Evidence indicating that the observed decrease in turbidity results from the release of cortical granule contents was obtained by correlating the free calcium ion concentration required to initiate the turbidity change with the free calcium ion concentration required in microscopic and enzymatic assays. All three assays exhibited similar calcium dependence. In the microscopic assay, morphological changes are used to assess the extent of cortical granule exocytosis. The enzymatic assay is based upon the latency of ovoperoxidase, a cortical granule enzyme. Ovoperoxidase catalyzed a 30-125-fold increase in the incorporation of [125I]iodine into trichloroacetic acid-precipitable cortex protein at and above threshold calcium ion concentrations. We have utilized the turbidimetric assay to screen several potential inhibitors of the cortical reaction. In confirmation of previous reports, we find that the phenothiazine drugs, chlorpromazine and trifluoperazine, are inhibitory. Sulfhydryl-modifying reagents, N-ethylmaleimide and sodium tetrathionate, are also inhibitory. Inhibition of cortical granule enzyme release by N-ethylmaleimide was confirmed with the ovoperoxidase latency assay.
我们开发了一种快速比浊法,用于检测从紫海胆(Strongylocentrotus purpuratus)卵制备的皮层中皮层颗粒内容物的释放。当游离钙离子浓度增加到0.38 - 0.62微摩尔时,皮层悬浮液的浊度降低,这可以通过分光光度法进行监测。动力学实验表明,这种钙触发的浊度变化迅速发生,且没有可检测到的延迟期。通过将引发浊度变化所需的游离钙离子浓度与显微镜和酶促测定所需的游离钙离子浓度相关联,获得了证据,表明观察到的浊度降低是由于皮层颗粒内容物的释放所致。所有三种测定都表现出相似的钙依赖性。在显微镜测定中,形态学变化用于评估皮层颗粒胞吐作用的程度。酶促测定基于卵过氧化物酶(一种皮层颗粒酶)的潜伏性。在阈值钙离子浓度及以上,卵过氧化物酶催化[125I]碘掺入三氯乙酸可沉淀的皮层蛋白中的量增加30 - 125倍。我们利用比浊法筛选了几种潜在的皮层反应抑制剂。正如之前报道所证实的,我们发现吩噻嗪类药物氯丙嗪和三氟拉嗪具有抑制作用。巯基修饰试剂N - 乙基马来酰亚胺和连四硫酸钠也具有抑制作用。通过卵过氧化物酶潜伏性测定证实了N - 乙基马来酰亚胺对皮层颗粒酶释放的抑制作用。