Charo I F, Feinman R D, Detwiler T C
J Clin Invest. 1977 Oct;60(4):866-73. doi: 10.1172/JCI108841.
The mechanism of stimulus-response coupling in human platelets was investigated with a new instrument that simultaneously monitors aggregation and secretion in the same sample of plateletrich plasma. When platelets were stimulated by high concentrations of ADP, secretion began only after aggregation was almost complete. With lower concentrations of ADP or with epinephrine, biphasic aggregation was observed, and secretion began simultaneously with, or slightly after, the second phase of aggregation. When platelets were stimulated with high concentrations of gamma-thrombin or A23187, secretion and aggregation began essentially together. With very low concentrations of gamma-thrombin or A23187, biphasic aggregation was observed with secretion paralleling the second phase. At every concentration of collagen, secretion and aggregation appeared to be parallel events. Under every condition where the beginning of secretion lagged behind aggregation, secretion was dependent upon aggregation and was inhibited by indomethacin; this is referred to as aggregation-mediated platelet activation. When secretion began at the same time as aggregation, it also occurred in the absence of aggregation and was not blocked by indomethacin; this is referred to as directly induced platelet activation. These observations are consistent with a simple model of platelet stimulus-response coupling that includes two mechanisms for activation; aggregation-mediated activation is inhibited by indomethacin, while direct activation does not depend upon aggregation and is not inhibited by indomethacin. Secretion and second wave aggregation appear to be parallel events, with little evidence for second wave aggregation being a consequence of secretion as usually described.
使用一种新仪器对人血小板中的刺激-反应偶联机制进行了研究，该仪器可同时监测富含血小板血浆同一样本中的聚集和分泌情况。当血小板受到高浓度二磷酸腺苷（ADP）刺激时，分泌仅在聚集几乎完成后才开始。使用较低浓度的ADP或肾上腺素时，观察到双相聚集，并且分泌在聚集的第二阶段同时或稍晚开始。当血小板受到高浓度γ-凝血酶或A23187刺激时，分泌和聚集基本同时开始。使用极低浓度的γ-凝血酶或A23187时，观察到双相聚集，分泌与第二阶段平行。在每种胶原浓度下，分泌和聚集似乎是平行发生的事件。在分泌开始落后于聚集的每种情况下，分泌依赖于聚集并被吲哚美辛抑制；这被称为聚集介导的血小板活化。当分泌与聚集同时开始时，它也在没有聚集的情况下发生，并且不被吲哚美辛阻断；这被称为直接诱导的血小板活化。这些观察结果与血小板刺激-反应偶联的简单模型一致，该模型包括两种活化机制；聚集介导的活化被吲哚美辛抑制，而直接活化不依赖于聚集且不被吲哚美辛抑制。分泌和第二波聚集似乎是平行事件，几乎没有证据表明第二波聚集是如通常所描述的分泌的结果。
