SERUM-ALBUMIN ENHANCES THE IMPAIRMENT OF PLATELET-AGGREGATION WITH THROMBOXANE SYNTHASE INHIBITION BY INCREASING THE FORMATION OF PROSTAGLANDIN-D2
SERUM-ALBUMIN ENHANCES THE IMPAIRMENT OF PLATELET-AGGREGATION WITH THROMBOXANE SYNTHASE INHIBITION BY INCREASING THE FORMATION OF PROSTAGLANDIN-D2
复制标题
DOI：
10.1016/0006-2952(84)90577-x
复制
发表时间：
1984-01-01
影响因子：
5.8
通讯作者：
VERMYLEN, J
中科院分区：
文献类型：
--
作者：
GRESELE, P;DECKMYN, H;VERMYLEN, J
血栓烷合酶抑制剂形成一类可供人类使用的新型抗血栓药物。 Dazoxiben 是一种血栓素合酶抑制剂，仅抑制某些供体（应答者）富含血小板的血浆中花生四烯酸诱导的聚集。研究了达佐昔苯体外对血小板聚集和前列腺素（PG）代谢的影响以及潜伏期和外源添加血清白蛋白（SA）的影响。 SA 增加了环状内过氧化物中抗聚集 PGD2 的产生，诱导无反应的人类血小板产生反应。对于对 PGD2 不敏感的兔血小板，外源 SA 未能增强达唑昔苯诱导的抑制作用。 PGD2 与形成的 TXB2 [血栓素 B2] + PGE2 之间的比率对于确定人血小板对达佐昔苯的反应至关重要；每当这个比率很高时，血小板聚集就会受到抑制。 SQ 22536 [9-(四氢-2-呋喃基)腺嘌呤]（一种腺苷酸环化酶抑制剂）和 NO164（一种 PGD2 拮抗剂）可逆转达佐昔本在人富含血小板血浆中的抑制作用，强调 PGD2 介导的 cAMP 升高对于血栓素合酶抑制剂有效性的重要性。
Thromboxane synthase inhibitors form a new class of antithrombotic drugs administrable to man. Dazoxiben, a thromboxane synthase inhibitor, inhibits arachidonic acid induced aggregation in platelet-rich plasma from some donors only (responders). The effect of dazoxiben in vitro on platelet aggregation and prostaglandin (PG) metabolism and the influence of the incubation period and of exogenously added serum albumin (SA), were studied. SA, which increases the production of anti-aggregatory PGD2 from cyclic endoperoxides, induced non-responder human platelets to respond. With rabbit platelets that are insensitive to PGD2, exogenous SA failed to potentiate dazoxiben-induced inhibition. The ratio between PGD2 and TXB2 [thromboxane B2] + PGE2 formed was crucial in determining the response of human platelets to dazoxiben; whenever this ratio was high, platelet aggregation was inhibited. SQ 22536 [9-(tetrahydro-2-furyl)adenine], an adenylate cyclase inhibitor, and NO164, a PGD2 antagonist, reversed the inhibition by dazoxiben in human platelet-rich plasma, stressing the importance of a PGD2 mediated rise of cAMP for the effectiveness of a thromboxane synthase inhibitor.