Soslau G, Youngprapakorn D
Department of Biochemistry, Medical College of Pennsylvania, Philadelphia, USA.
Biochim Biophys Acta. 1997 Feb 4;1355(2):131-40. doi: 10.1016/s0167-4889(96)00123-1.
ATP and ADP are simultaneously released from activated platelets in equimolar concentrations. Micromolar concentrations of ATP inhibit platelet aggregation by both competitive and non-competitive mechanisms. The current studies addressed the question of how platelets respond to agonists in the presence of nanomolar and micromolar concentrations of ATP and ADP alone or in combination. This is a significant issue since the concentration of ATP +/- ADP may vary widely within a microenvironment depending upon the source and cause for the release of the nucleotides. ATP (1-10 nM) was found to significantly enhance the thromboxane A2 analog, U44619-, collagen- and thrombin-induced platelet aggregations. Conversely, ATP at 1-100 microM inhibited these same reactions. ADP, in general, behaved exactly opposite to ATP. When equal amounts of ATP and ADP were added together the ADP response appeared to predominate. The observed ATP-induced response was not due to a hydrolytic product as evidenced by an unaltered response to ATP in the presence of adenosine deaminase or the ATP generating system, creatine phosphate plus creatine phosphokinase. Adenosine (1-10 nM), like ADP, inhibited agonist-induced platelet aggregation. The stimulation of agonist-induced platelet aggregation by 1-10 nM extracellular ATP appears to depend upon the phosphorylation of platelet membrane ecto proteins. The ATP analog, beta gamma-methylene ATP, that is incapable of serving as a phosphate donor for protein kinases, inhibited rather than stimulated agonist-induced platelet aggregation. The dual response of platelets to low and high concentrations of extracellular ATP +/- ADP may play a physiological role in hemostasis and thrombosis under normal and pathological conditions.
三磷酸腺苷（ATP）和二磷酸腺苷（ADP）以等摩尔浓度同时从活化的血小板中释放出来。微摩尔浓度的ATP通过竞争性和非竞争性机制抑制血小板聚集。目前的研究探讨了在单独或组合存在纳摩尔和微摩尔浓度的ATP和ADP的情况下，血小板如何对激动剂作出反应。这是一个重要问题，因为根据核苷酸释放的来源和原因，微环境中ATP±ADP的浓度可能有很大差异。发现ATP（1 - 10 nM）能显著增强血栓素A2类似物U44619、胶原和凝血酶诱导的血小板聚集。相反，1 - 100 μM的ATP抑制这些相同的反应。一般来说，ADP的表现与ATP完全相反。当加入等量的ATP和ADP时，ADP的反应似乎占主导。观察到的ATP诱导反应不是由于水解产物，这在腺苷脱氨酶或ATP生成系统（磷酸肌酸加磷酸肌酸激酶）存在下对ATP的反应未改变得到证明。腺苷（1 - 10 nM）与ADP一样，抑制激动剂诱导的血小板聚集。1 - 10 nM细胞外ATP对激动剂诱导的血小板聚集的刺激似乎取决于血小板膜外蛋白的磷酸化。不能作为蛋白激酶磷酸供体的ATP类似物βγ - 亚甲基ATP抑制而不是刺激激动剂诱导的血小板聚集。血小板对低浓度和高浓度细胞外ATP±ADP的双重反应可能在正常和病理条件下的止血和血栓形成中发挥生理作用。
