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

为了阐明我们于1980-1981年报道的一种新型血小板释放机制异常的缺陷机制，用水母发光蛋白负载法分析了凝血酶、A23187、稳定血栓烷类似物SAT_2和花生四烯酸诱导的血小板胞内Ca ~（++）、[Ca ~（+）]i。在存在L mM Ca^++>的情况下，患者（P）血小板显示响应于凝血酶的正常[Ca^++]i升高（流入和细胞内动员），但抑制低浓度的A23187或STA_2。在缺乏Ca^<++>的情况下，通过加入2 mM Ca^<++>或通过肾上腺素增强，减少的动员增强到正常。TMB-8在正常血小板中引起类似于P血小板的聚集减少，对肾上腺素增强不敏感。Bernard-Soulier综合征、环氧合酶缺乏症和Hermansky-Pudlak综合征均有不同程度的[Ca^++]i动员异常，表明本方法测定的Ca^++动员具有不同的特点。P血小板对A23187或STA_2的Ca ~（++）动员有部分缺陷（可能是Ca ~（++）内流），与TMB-8处理的正常血小板不同。[Ca^<++>]i动员与各种激动剂的聚集或释放之间的密切关系有待研究。

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.