Role of 5-hydroxytryptamine in platelet thrombus formation and mechanisms of inhibition of thrombus formation by 5-hydroxytryptamine2A antagonists in rabbits.
Role of 5-hydroxytryptamine in platelet thrombus formation and mechanisms of inhibition of thrombus formation by 5-hydroxytryptamine2A antagonists in rabbits.
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5-羟色胺在兔血小板血栓形成中的作用以及5-羟色胺2A拮抗剂抑制血栓形成的机制。
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发表时间：
1995
影响因子：
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通讯作者：
S. Takano
中科院分区：
文献类型：
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作者：
S. Takano
使用比浊法研究了 5-羟色胺 (5-HT) 在血小板血栓形成中的作用以及在 5-HT2A 拮抗剂抑制血栓形成的机制中的作用。胶原诱导的血小板聚集与血小板释放 5-HT 同时发生。胶原聚集的血小板的上清液诱导体积依赖性的进一步聚集。这种上清液诱导的聚集可被 5-HT2A 拮抗剂或二磷酸腺苷 (ADP) 清除抑制。 5-羟色胺和少量上清液使胶原蛋白的剂量反应曲线向左移动。上清液显着增加了胶原蛋白的聚集速度和聚集起始时间，但 5-HT 则没有显着增加。 5-HT2A拮抗剂酮色林和MCI-9042使已经被上清液放大的胶原蛋白的最大聚集和聚集速度的剂量反应曲线恢复到原始值。聚集的开始被拮抗剂延迟，但没有完全返回到原始点。源自胶原蛋白刺激的血小板的内源性 5-HT 与外源性 5-HT 对广泛的血小板活化和胶原诱导的聚集放大的影响存在明显差异。这些发现表明内源性 5-HT 与 ADP 协同激活血小板。使用的 5-HT2A 拮抗剂通过 5-HT2A 受体阻断协同作用，并导致血栓形成的正反馈回路受到抑制。
The role of 5-hydroxytryptamine (5-HT) in platelet thrombus formation and in the mechanisms of inhibition of thrombus formation by 5-HT2A antagonists was investigated using a turbidimetric method. Collagen-induced platelet aggregation occurred simultaneously with a release of 5-HT from the platelets. The supernatant of collagen-aggregated platelets induced a further aggregation volume-dependently. This supernatant-induced aggregation was inhibited by either 5-HT2A antagonists or adenosine-diphosphate (ADP) scavenging. 5-Hydroxytryptamine and a small amount of the supernatant shifted the dose-response curves of collagen to the left. The aggregation velocity and the onset of aggregation by collagen were significantly increased by the supernatant, but not by 5-HT. The 5-HT2A antagonists, ketanserin and MCI-9042, returned the dose-response curves of the maximum aggregation and of the aggregation velocity of collagen, which were already amplified by the supernatant, to the original values. The onset of aggregation was delayed by the antagonists, but was not completely returned to the original points. There were distinct differences between the effects of endogenous 5-HT, derived from platelets which were stimulated by collagen, and those of exogenous 5-HT on both extensive platelet activation and amplification of the collagen-induced aggregation. These findings suggest that endogenous 5-HT activates platelets in synergism with ADP. The 5-HT2A antagonists used, block the synergism via 5-HT2A receptors and lead to inhibition of a positive feedback loop of thrombus formation.