Ko F N, Wu C C, Kuo S C, Lee F Y, Teng C M
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Blood. 1994 Dec 15;84(12):4226-33.
YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] inhibited the aggregation of and ATP release from washed rabbit platelets induced by arachidonic acid (AA), collagen, U46619, platelet-activating factor (PAF), and thrombin in a concentration-dependent manner. YC-1 also disaggregated the clumped platelets caused by these inducers. The thromboxane B2 formation caused by collagen, PAF, and thrombin was inhibited by concentrations of YC-1 that did not affect formation of thromboxane B2 and prostaglandin D2 caused by AA. YC-1 suppressed the increase of intracellular Ca2+ concentration and generation of inositol 1,4,5-trisphosphate caused by these five aggregation inducers. Both the cAMP and cGMP contents of platelets were increased by YC-1 in a concentration- and time-dependent manner. Like sodium nitroprusside, YC-1 potentiated formation of cAMP caused by prostaglandin E1 but not that by 3-isobutyl-1-methylxanthine. Adenylate cyclase and cAMP phosphodiesterase activities were not altered by YC-1. Activity of cGMP phosphodiesterase was unaffected by YC-1. Activities of guanylate cyclase in platelet homogenate and cytosolic fraction were activated by YC-1, whereas particulate guanylate cyclase activity was unaffected. The antiplatelet effect of sodium nitroprusside but not that of YC-1 was blocked by hemoglobin and potentiated by superoxide dismutase. After intraperitoneal administration for 30 minutes, YC-1 prolonged the tail bleeding time of conscious mice. These data indicate that YC-1 is a direct soluble guanylate cyclase activator in rabbit platelets. It may also possess antithrombotic potential in vivo.
YC-1[3-(5'-羟甲基-2'-呋喃基)-1-苄基吲唑]以浓度依赖的方式抑制花生四烯酸（AA）、胶原、U46619、血小板活化因子（PAF）和凝血酶诱导的洗涤兔血小板的聚集和ATP释放。YC-1还使这些诱导剂引起的聚集血小板解聚。胶原、PAF和凝血酶引起的血栓素B2形成受到YC-1浓度的抑制，而该浓度不影响AA引起的血栓素B2和前列腺素D2的形成。YC-1抑制这五种聚集诱导剂引起的细胞内Ca2+浓度升高和肌醇1,4,5-三磷酸的生成。YC-1以浓度和时间依赖的方式增加血小板的cAMP和cGMP含量。与硝普钠一样，YC-1增强前列腺素E1引起的cAMP形成，但不增强3-异丁基-1-甲基黄嘌呤引起的cAMP形成。YC-1不改变腺苷酸环化酶和cAMP磷酸二酯酶的活性。cGMP磷酸二酯酶的活性不受YC-1影响。YC-1激活血小板匀浆和胞质部分的鸟苷酸环化酶活性，而微粒体鸟苷酸环化酶活性不受影响。血红蛋白可阻断硝普钠的抗血小板作用，但不阻断YC-1的抗血小板作用，超氧化物歧化酶可增强其作用。腹腔注射30分钟后，YC-1延长清醒小鼠的尾部出血时间。这些数据表明，YC-1是兔血小板中一种直接的可溶性鸟苷酸环化酶激活剂。它在体内也可能具有抗血栓形成的潜力。
