YC-1, A NOVEL ACTIVATOR OF PLATELET GUANYLATE-CYCLASE
YC-1, A NOVEL ACTIVATOR OF PLATELET GUANYLATE-CYCLASE
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DOI：
10.1182/blood.v84.12.4226.bloodjournal84124226
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发表时间：
1994-12-15
期刊：
影响因子：
20.3
通讯作者：
TENG, CM
中科院分区：
文献类型：
--
作者：
KO, FN;WU, CC;TENG, CM
YC-1 [3-（5 ′-羟甲基-2 ′-呋喃基）-1-苄基吲唑]对花生四烯酸（AA）、胶原、U46619、血小板活化因子（PAF）和凝血酶诱导的兔血小板聚集和ATP释放有浓度依赖性抑制作用，YC-1对上述诱导剂诱导的血小板聚集也有解聚作用。YC-1浓度对凝血酶有抑制作用，但不影响AA引起的血栓素B-2和前列腺素D-2的形成。YC-1可抑制这5种聚集诱导剂引起的细胞内Ca ~（2+）浓度升高和1，4，5-三磷酸肌醇的生成。YC-1可使血小板cAMP和cGMP含量增加，并呈浓度和时间依赖性。与硝普钠类似，YC-1可增强前列腺素E（1）引起的cAMP生成，但对3-异丁基-1-甲基黄嘌呤无此作用。YC-1对腺苷酸环化酶和cAMP磷酸二酯酶活性无影响，对cGMP磷酸二酯酶活性无影响。YC-1可激活血小板匀浆和胞浆中鸟苷酸环化酶的活性，而颗粒鸟苷酸环化酶的活性则不受影响。硝普钠的抗血小板作用可被血红蛋白阻断，而YC-1的抗血小板作用则不受影响。YC-1腹腔给药30分钟后，可延长清醒小鼠尾部出血时间，这些数据表明，YC-1是一个直接可溶性鸟苷酸环化酶激活剂在兔血小板。它也可能具有体内抗血栓形成的潜力。(C)1994年，美国血液学会。
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 B-2 formation caused by collagen, PAF, and thrombin was inhibited by concentrations of YC-1 that did not affect formation of thromboxane B-2 and prostaglandin D-2 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 E(1) 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. (C) 1994 by The American Society of Hematology.