Lasslo A, Quintana R P, Johnson R W, Naylor J L, Dugdale M
Biochim Biophys Acta. 1984 Apr 25;772(1):84-92. doi: 10.1016/0005-2736(84)90520-0.
Gradually altered synthetic entities were employed as molecular probes, and arachidonic acid, ADP, human alpha-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 microM 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.
在一项关于人血小板反应谱的全面研究中，逐渐改变的合成实体被用作分子探针，花生四烯酸、ADP、人α - 凝血酶和Ca2+离子载体A23187被用作聚集诱导剂，该研究重点关注外源性和细胞内Ca2+增加的影响。进一步证实了先前的结论，一些代表性的氨基甲酰哌啶衍生物在能有效抑制ADP诱导聚集的浓度下，当向其他条件相同的测试介质中引入5.0 mM Ca2+时，无法保持该抑制作用；参考化合物氯丙嗪和普萘洛尔呈现出相应的抑制模式。在较高浓度下，即使存在5 mM Ca2+，化合物的抑制效力也能恢复。事实上，在足够高的浓度下，这些化合物甚至能够抑制由15 μM离子载体A23187引发的聚集；氯丙嗪和普萘洛尔也是如此。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显著敏感性。抑制效力的丧失与分子疏水性降低直接相关。
