Relationships between the chemical constitution of aggregation inhibitors and human blood platelet response profile.
Relationships between the chemical constitution of aggregation inhibitors and human blood platelet response profile.
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聚集抑制剂的化学组成与人血小板反应谱之间的关系。
DOI：
10.1016/0005-2736(84)90520-0
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Dugdale,M
中科院分区：
文献类型：
--
作者：
Lasslo,A;Quintana,RP;Johnson,RW;Naylor,JL;Dugdale,M
以逐渐改变的合成实体为分子探针，花生四烯酸、ADP、人α-凝血酶和Ca2+离子载体A23187为聚集诱导剂，综合研究了人血小板的反应谱，重点研究了外源性和细胞内Ca2+增加的影响。进一步证实了先前的结论，一些具有代表性的氨基甲酰哌啶衍生物，在浓度对adp诱导的聚集有实质性抑制作用时，当5.0 mM Ca2+被引入其他相同的测试介质中时，未能保持这种效果；对照物氯丙嗪和心得安有相应的抑制模式。在浓度增加时，即使在5 mM Ca2+的存在下，化合物的抑制效力也会再生。事实上，在足够高的浓度下，化合物甚至能够抑制15 μM离子载体A23187引起的聚集；氯丙嗪和心得安也是如此。另一组同系物揭示了离子载体a23187诱导的人血小板聚集对抑制剂分子表面活性的惊人敏感性。抑制效力的丧失与分子的疏水性较弱直接相关。
Gradually altered synthetic entities were employed as molecular probes, and arachidonic acid, ADP, human α-thrombin and the Ca2+ionophore A23187 as aggregation-inducing agents, in a comprehensive study on the response profile of human blood platelets with an emphasis on the effects of exogenous and increased intracellular Ca2+. Corroborating further previous conclusions, some representative carbamoylpiperidine derivatives, at concentrations effecting substantial inhibition of ADP-induced aggregation, failed to retain that effect when 5.0 mM Ca2+was introduced into the otherwise identical test medium; reference compounds chlorpromazine and propranolol registered corresponding inhibitory patterns. At increased concentrations the compounds' inhibitory potency was regenerated even in the presence of 5 mM Ca2+. In fact, in sufficiently high concentrations, the compounds were even capable of inhibiting aggregation elicited by 15 μM of the ionophore A23187; so did chlorpromazine and propranolol. Another set of congeners revealed the striking sensitivity of ionophore A23187-induced human blood platelet aggregation to the surface active potencies of inhibitor molecules. The loss in inhibitory potency was directly related to the lesser hydrophobic character of the molecule.