Ushikubi F, Okuma M, Kanaji K, Sugiyama T, Ogorochi T, Narumiya S, Uchino H
Thromb Haemost. 1987 Apr 7;57(2):158-64.
Subnormal platelet responses to thromboxane A2 (TXA2) were found in a patient with polycythemia vera, and the mechanism of this dysfunction was analyzed. The patient's platelets showed defective aggregation and release reaction to arachidonic acid, enzymatically generated TXA2 and synthetic TXA2 mimetics (STA2, U-46619). In contrast, they showed normal responses to thrombin. When the platelet TXA2 receptor was examined with both a 125I-labelled derivative of a TXA2 receptor antagonist ([125I]-PTA-OH) and a 3H-labelled TXA2 agonist ([3H]U-46619), the equilibrium dissociation rate constants (Kd) and the maximal concentrations of binding sites (Bmax) of the patient's platelets to both ligands were within normal ranges, suggesting that the binding capacity of their TXA2 receptor was normal. STA2 failed to induce normal elevation in the cytoplasmic free calcium ion concentration, phosphatidic acid formation and 40 kD protein phosphorylation in the patient's platelets, whereas these responses to thrombin were within normal ranges. 12-O-Tetradecanoyl-phorbol-13-acetate (TPA) also evoked normal response in the 40 kD protein phosphorylation in the patient's platelets. These results suggested that the patient's platelets had TXA2 receptor abnormalities which were characterized by defective transduction of the binding signal to postreceptor reactions after normal TXA2 binding.
在一名真性红细胞增多症患者中发现血小板对血栓素A2（TXA2）反应低下，并对这种功能障碍的机制进行了分析。该患者的血小板对花生四烯酸、酶促生成的TXA2和合成TXA2类似物（STA2、U-46619）的聚集和释放反应存在缺陷。相比之下，它们对凝血酶的反应正常。当用TXA2受体拮抗剂的125I标记衍生物（[125I]-PTA-OH）和3H标记的TXA2激动剂（[3H]U-46619）检测血小板TXA2受体时，患者血小板对两种配体的平衡解离速率常数（Kd）和结合位点的最大浓度（Bmax）均在正常范围内，表明其TXA2受体的结合能力正常。STA2未能在患者血小板中诱导正常的细胞质游离钙离子浓度升高、磷脂酸形成和40 kD蛋白磷酸化，而这些对凝血酶的反应在正常范围内。12-O-十四酰佛波醇-13-乙酸酯（TPA）在患者血小板中也能引起40 kD蛋白磷酸化的正常反应。这些结果表明，该患者的血小板存在TXA2受体异常，其特征是在正常TXA2结合后，结合信号向受体后反应的转导存在缺陷。
