Platelet shape change and Ca2+ mobilization induced by collagen, but not thrombin or ADP, are inhibited by phenylarsine oxide.
Platelet shape change and Ca2+ mobilization induced by collagen, but not thrombin or ADP, are inhibited by phenylarsine oxide.
复制标题
氧化苯胂会抑制胶原蛋白（而非凝血酶或 ADP）诱导的血小板形状变化和 Ca2 动员。
DOI：
10.1111/j.1365-2141.1994.tb05124.x
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发表时间：
1994
影响因子：
6.5
通讯作者：
Tandon,NN
中科院分区：
文献类型：
--
作者：
Greenwalt,DE;Tandon,NN
在这份报告中，我们研究了蛋白酪氨酸磷酸酶抑制剂氧化苯胂（PAO）对受体介导的血小板形状改变、分泌和聚集的影响。PAO抑制胶原、凝血酶、ADP和肾上腺素诱导的血小板聚集，IC_（50）分别为0.35 μmol/l、2.5 μmol/l、0.2 μmol/l和0.3 μmol/l。在相似或较低浓度的PAO下，激动剂诱导的ATP分泌受到抑制。PAO与血小板蛋白相互作用的特异性通过二巯基化合物2，3-二巯基丙醇（其从蛋白质中提取PAO以形成稳定的环状加合物）逆转PAO对激动剂诱导的血小板分泌和聚集的抑制的能力来证明。二巯基丙磺酸（二巯基丙醇的一种膜不可渗透类似物）未逆转PAO对胶原诱导的形状变化或聚集的抑制作用，从而证明PAO在细胞内起作用。PAO抑制胶原诱导的形状变化和内部Ca 2+动员，但在凝血酶或ADP诱导时对这两种现象没有影响。PAO也不能阻止花生四烯酸诱导的形状变化，表明PAO作用于磷脂酶A2介导的花生四烯酸释放之前的部位，以抑制胶原诱导的形状变化。PAO诱导了大量含磷酸酪氨酸蛋白的积累，并抑制了胶原诱导的40 kD蛋白的磷酸化。PAO对血小板活化的效力和激动剂特异性作用表明，这种抑制剂在阐明受体介导的血小板功能所涉及的信号转导途径方面具有价值。
In this report we have examined the effects of the protein tyrosine phosphatase inhibitor phenylarsine oxide (PAO) on receptor‐mediated platelet shape change, secretion and aggregation. PAO was found to inhibit platelet aggregation induced by collagen, thrombin, ADP and epinephrine at IC50values of 0.35 μmol/l, 2.5 μmol/l, 0.2 μmol/l and 0.3 μmol/l, respectively. Agonist‐induced secretion of ATP was inhibited at similar or lower concentrations of PAO. The specificity of the interaction of PAO with platelet proteins was demonstrated by the ability of the disulfhydryl compound 2,3‐dimercaptopropanol, which abstracts PAO from proteins to form a stable cyclic adduct, to reverse PAO inhibition of both agonist‐induced platelet secretion and aggregation. Dimercaptopropanesulphonic acid, a membrane‐impermeable analogue of dimercaptopropanol, did not reverse inhibition of collagen‐induced shape change or aggregation by PAO, thereby demonstrating that PAO acted intracellularly. PAO inhibited collagen‐induced shape change and internal Ca2+mobilization but had no effect on these two phenomena when induced by thrombin or ADP. PAO was also unable to prevent arachidonic acid‐induced shape change, indicating that PAO acts at a site prior to the phospholipase A2‐mediated release of arachidonic acid to inhibit collagen‐induced shape change. PAO induced the accumulation of a number of phosphotyrosine‐containing proteins and inhibited the collagen‐induced phosphorylation of a 40 kD protein. The potency and agonist‐specific effects of PAO on platelet activation suggest that this inhibitor will be of value in elucidation of signal transduction pathways involved in receptor‐mediated platelet function.