碱性磷酸酶可防止血小板受到血栓素模拟物的刺激。

Alkaline phosphatase prevents platelet stimulation by thromboxane-mimetics.

作者信息

Hatmi M, Haye B, Gavaret J M, Vargaftig B B, Jacquemin C

机构信息

Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur/INSERM No. 285, Paris, France.

出版信息

Br J Pharmacol. 1991 Oct;104(2):554-8. doi: 10.1111/j.1476-5381.1991.tb12467.x.

DOI:10.1111/j.1476-5381.1991.tb12467.x

PMID:1665743

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908576/

Abstract

The effects of alkaline phosphatase on platelet aggregation, secretion and thromboxane B2 (TxB2) generation induced by the full dose-range of common platelet agonists were studied in human platelet-rich plasma and washed platelets. 2. Platelet aggregation and adenosine 5'-triphosphate (ATP) secretion induced by threshold and supramaximal concentrations of arachidonate and stable TxA2 and prostaglandin endoperoxide-mimetics (compounds U46619 and EP171) were abolished in the presence of alkaline phosphatase (0.5-1 u ml-1), even though the synthesis of TxB2 persisted. In contrast, platelet aggregation by PAF-acether and by supramaximal concentrations of thrombin as well as the primary wave of aggregation by adenosine diphosphate (ADP) and adrenaline were unaffected by alkaline phosphatase under conditions where the secondary wave of aggregation by ADP was blocked. 3. Alkaline phosphatase, unlike prostacyclin, failed to raise the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content of the platelets. Also, the pretreatment of platelets by inorganic phosphate or by ATP plus creatine phosphate/creatine phosphokinase reversed the inhibitory effect of alkaline phosphatase. 4. Experiments performed in the guinea-pig in vivo showed that alkaline phosphatase was effective on thrombocytopenia induced by arachidonate. 5. Our results provide the first direct evidence for a specific inhibitory effect of alkaline phosphatase at a site sensitive to TxA2 and prostaglandin endoperoxides and suggest that its phosphorylation/dephosphorylation state may play an important role in modulating platelet activation. These results also suggest the presence of ecto-protein kinases on membrane platelets.

摘要

在富含人血小板的血浆和洗涤后的血小板中，研究了碱性磷酸酶对常见血小板激动剂全剂量范围诱导的血小板聚集、分泌及血栓素B2（TxB2）生成的影响。2. 在碱性磷酸酶（0.5 - 1单位/毫升）存在的情况下，花生四烯酸、稳定的TxA2及前列腺素内过氧化物模拟物（化合物U46619和EP171）的阈值浓度和超最大浓度诱导的血小板聚集及三磷酸腺苷（ATP）分泌被消除，尽管TxB2的合成持续存在。相比之下，在ADP的二次聚集波被阻断的条件下，PAF - 乙酰醚、超最大浓度凝血酶诱导的血小板聚集以及二磷酸腺苷（ADP）和肾上腺素诱导的初次聚集波不受碱性磷酸酶影响。3. 与前列环素不同，碱性磷酸酶未能提高血小板的3':5'-环磷酸腺苷（环磷酸腺苷）含量。此外，用无机磷酸盐或ATP加磷酸肌酸/肌酸磷酸激酶对血小板进行预处理可逆转碱性磷酸酶的抑制作用。4. 在豚鼠体内进行的实验表明，碱性磷酸酶对花生四烯酸诱导的血小板减少有效。5. 我们的结果首次直接证明了碱性磷酸酶在对TxA2和前列腺素内过氧化物敏感的位点具有特异性抑制作用，并表明其磷酸化/去磷酸化状态可能在调节血小板活化中起重要作用。这些结果还提示膜血小板上存在胞外蛋白激酶。