FIBRINOGEN RECEPTORS IN HEREDITARY THROMBOPATHIA

犬血栓病(BHT)是一种遗传性缺陷。 有严重出血性素质的纯种狗。在……里面 初步研究，糖蛋白IIb-IIIa含量，125标记 纤维蛋白原结合，金标记纤维蛋白原结合，电子 显微形态、血小板计数和凝块回缩 被发现是正常的。BHT血小板的聚集不会 发生于二磷酸腺苷(ADP)、血小板 激活因子(PAF)或A23187是可逆的 肾上腺素；对佛波醇肉豆蔻的完全反应 醋酸酯(PMA)或凝血酶浓度大于0.1 U/ml。凝血酶诱导致密颗粒内容物释放 PMA是正常的，但A23187和肾上腺素都不能诱导 意义重大的发布。ADP和PAF诱导正常血浆释放 三磷酸腺苷的量，但释放速率增加。这些 结果表明，BHT只聚集和释放血小板 当磷脂酰肌醇的水解途径可以被绕过时。 工作假说提出，在 肌醇磷脂第二信使系统。在预赛中 Quin-2负载细胞内钙离子(Ca2+)通量的研究 与ADP、PAF、凝血酶或A23187孵育的血小板 很正常。 为有条不紊地研究这些途径而设计的具体目标 包括进一步测量细胞质 Ca2+通量，蛋白激酶C影响的评估 抑制剂H-7，血栓素A2产生的测定， 20和40-47 kDa蛋白磷酸化的鉴定、分离 蛋白激酶C的二酰甘油产量的测定 和磷脂酶A2的分离。该计划的总体目标是 是为了刻画分子异常导致的 BHT和TO患者的血小板聚集和分泌缺陷 研究脑电刺激-反应耦合现象 血小板。

Basset Hound thrombopathy (BHT) is a hereditary defect in linebred dogs in which there is a severe hemorrhagic diathesis. In initial studies, glycoprotein IIb-IIIa content, 125-labeled fibrinogen binding, gold-labeled fibrinogen binding, electron micrographic morphology, platelet counts and clot retraction were found to be normal. Aggregation of BHT platelets does not occur in response to adenosine diphosphate (ADP), platelet activating factor (PAF), or A23187; is reversible in response to epinephrine; and complete in response to phorbol myristate acetate (PMA) or concentrations of thrombin greater than 0.1 U/ml. Release of dense granule contents induced by thrombin or PMA is normal but neither A23187 or epinephrine is able to induce significant release. ADP and PAF induce release of a normal quantity of ATP, but the rate of release is increased. These results suggest that BHT platelets aggregate and release only when the phospho-inositide hydrolysis pathway can be bypassed. The working hypothesis proposes that there is a defect in the inositol phospholipid second messenger system. In preliminary studies, cytoplasmic ionized Ca2+ (Cai2+) fluxes in Quin 2-loaded platelets incubated with ADP, PAF, thrombin or A23187 are normal. Specific aims designed to methodically investigate the pathways of platelet activation include further measurement of cytoplasmic Cai2+ fluxes, assessment of the effects of the protein kinase C inhibitor H-7, measurement of thromboxane A2 production, assessment of 20 and 40-47 kDa protein phosphorylation, isolation of protein kinase C, measurement of diacylglycerol production and isolation of phospholipase A2. The overall aim of the program is to characterize the molecular abnormality responsible for the platelet aggregation and secretion defect in BHT and to investigate the stimulus-response coupling phenomena in the platelet.