Soslau G, Arabe L, Parker J, Pelleg A
Department of Biological Chemistry, Hahnemann University, Philadelphia, PA 19102-1192.
Thromb Res. 1993 Oct 15;72(2):127-37. doi: 10.1016/0049-3848(93)90214-9.
This study compared the responses of canine and human platelets to various aggregating agonists in the presence or absence of extracellular ATP and ATP analogues. Canine and human platelets were approximately equally reactive with ADP or collagen while the canine platelets were about 10 fold more sensitive to thrombin. Canine platelets were insensitive to the thromboxane mimetic U46619 but were synergistically aggregated by a mixture of ADP and U46619. Human platelets were very sensitive to U46619. Aggregations of human platelets with all of the above agonists were inhibited by extracellular ATP; beta, gamma methylene ATP (beta gamma ATP) and benzoyl ATP (BzATP) with a rank order suggestive of an interaction with P2x-like purinoceptors which support our previous findings. The comparable aggregations of canine platelets were likewise inhibited by ATP and its analogues but with a rank order suggestive of an interaction with P2y-like purinoceptors. ATP inhibited U46619- and ADP-induced aggregation of human platelets and ADP-induced aggregation of canine platelets, presumably, in part, due to competition for the ADP P2T receptor. However, when U46619 was added to either ATP or ATP analogue-inhibited ADP-treated canine platelets, the inhibition was nullified. Furthermore, we demonstrated, for the first time, that the canine thromboxane receptor becomes reactive to U46619 alone after incubation at room temperature for 3.5-5 hrs while human platelets become inactive under similar conditions. The implication of these studies is that there are significant differences in the canine and human platelet thromboxane and purine receptors. The future characterization of these differences and the mechanism by which they function should further our understanding of the impact of extracellular ATP on hemostasis and thrombosis.
本研究比较了犬类和人类血小板在存在或不存在细胞外ATP及ATP类似物的情况下，对各种聚集激动剂的反应。犬类和人类血小板对ADP或胶原的反应性大致相同，而犬类血小板对凝血酶的敏感性约高10倍。犬类血小板对血栓素类似物U46619不敏感，但对ADP和U46619的混合物有协同聚集作用。人类血小板对U46619非常敏感。细胞外ATP可抑制上述所有激动剂诱导的人类血小板聚集；β,γ-亚甲基ATP（βγATP）和苯甲酰ATP（BzATP）的抑制作用顺序表明其与P2x样嘌呤受体相互作用，这支持了我们之前的研究结果。犬类血小板的类似聚集同样受到ATP及其类似物的抑制，但抑制作用顺序表明其与P2y样嘌呤受体相互作用。ATP抑制U46619和ADP诱导的人类血小板聚集以及ADP诱导的犬类血小板聚集，推测部分原因是其与ADP P2T受体竞争。然而，当将U46619添加到ATP或ATP类似物抑制的ADP处理的犬类血小板中时，抑制作用消失。此外,我们首次证明，犬类血栓素受体在室温下孵育3.5 - 5小时后对单独的U46619有反应，而人类血小板在类似条件下则失去活性。这些研究表明，犬类和人类血小板血栓素和嘌呤受体存在显著差异。对这些差异及其作用机制的进一步表征，应有助于我们更好地理解细胞外ATP对止血和血栓形成的影响。
