Study on a new release mechanism abnormality (unresponsiveness to thromboxane A_2) of platelet

为了阐明我们在1980-1981年报道的一种新型血小板释放机制异常的缺陷机制，我们分析了凝血酶A23187、稳定的血栓素类似物SAT_2或aequorin加载法诱导的细胞内Ca^<++>,[Ca^<++>]i的动员情况。L mM Ca^<++>存在时，患者(P)血小板对凝血酶的反应是正常的[Ca^<++>]i升高（内流和细胞内动员），但对低浓度的A23187或STA_2有抑制作用。在缺乏Ca^<++>的情况下，通过添加2mM Ca^<++>或肾上腺素增强，使活动减少恢复正常。TMB-8对肾上腺素增强不敏感，其引起的聚集减少与正常血小板中的P血小板相似。在Bernard-Soulier综合征、环氧化酶缺乏症和Hermansky-Pudlak综合征中发现不同程度的[Ca^<++>]动员异常，提示本方法测量的Ca^<++>动员特征不同。结论：在A23187或STA_2作用下，P血小板在Ca^<++>动员方面存在部分缺陷（可能是Ca内流），与TMB-8处理的正常血小板不同。[Ca^<++>]i的动员与各种激动剂的聚集或释放之间的密切关系有待进一步研究。

In order to clarify the mechanism of defect in a new type of platelet release mechanism abnormality reported by us in 1980-1981, intracellular Ca^<++>,[Ca^<++>]i, mobilization was analysed in cases of thrombin, A23187, stable thromboxane analog SAT_2 or arachidonate-induction using aequorin loading method. In presence of L mM Ca^<++>, patient (P) platelets showed normal [Ca^<++>]i elevation (influx and intracellular mobilization) in response to thrombin, but suppressed one to low concentration of A23187 or STA_2. The decreased mobilization in absence of Ca^<++> was enhanced to normal by addition of 2mM Ca^<++> or by adrenalin potentiation. TMB-8 which caused reduced aggregation similar to P platelets in normal platelets was not sensitive to adrenalin potentiation. Various but slight degree of abnormalities in [Ca^<++>]i mobilization were found in Bernard-Soulier syndrome, cyclooxygenase deficiency, and Hermansky-Pudlak syndrome, suggestkng different characters of Ca^<++> mobilization measured by present method. In conclusion P platelets were partially defective in Ca^<++> mobilization (probably Ca influx) in responses to A23187 or STA_2, and different from TMB-8 treated normal paltelets. Closer relation between[Ca^<++>]i mobilization and aggregation or release in various agonists is neccessary to be investigated.