Inhibition of Human Platelet Aggregation and Cytoplasmic Calcium Response by Calcium Antagonists: Studies with Aequorin and Quin2
Inhibition of Human Platelet Aggregation and Cytoplasmic Calcium Response by Calcium Antagonists: Studies with Aequorin and Quin2
复制标题
钙拮抗剂抑制人血小板聚集和细胞质钙反应：水母发光蛋白和 Quin2 的研究
DOI：
10.1161/01.res.59.1.39
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发表时间：
1986
影响因子：
20.1
通讯作者：
E. Salzman
中科院分区：
文献类型：
--
作者：
J. Ware;P. Johnson;Marianne Smith;E. Salzman
钙拮抗剂抑制血小板聚集，但这种作用是否是由于抑制激动剂对细胞质离子钙浓度的影响尚不清楚。我们研究了这个问题，通过加载凝胶过滤的血小板与quin 2或水母发光蛋白和刺激他们与肾上腺素，花生四烯酸，凝血酶，钙离子载体A23187，l-油酰基-2-乙酰甘油，或腺苷二磷酸在培养基中有或没有细胞外钙。在对所有这些激动剂的反应中，水母发光蛋白指示伴随或先于血小板聚集的细胞质钙的增加。在含钙介质中，维拉帕米，硝苯地平，和地尔硫卓抑制这些作用的浓度依赖性的方式，除了凝血酶和A23187产生的。用EGTA去除细胞外钙降低了对花生四烯酸、腺苷二磷酸和L-油酰-2-乙酰甘油的钙响应，并且钙响应和聚集被钙拮抗剂进一步抑制。一般而言，约100 μM浓度的硝苯地平、维拉帕米和地尔硫卓对水母发光蛋白胞质钙信号的强烈抑制与血小板聚集的抑制相关，但需要高浓度的抑制剂。由于钙拮抗剂对细胞质钙反应和聚集的抑制作用超过了简单清除细胞外钙的作用，因此这些药物可能影响人血小板中钙的内部再分布。
Calcium antagonists inhibit platelet aggregation, but whether this action is due to inhibition of the effect of agonists on cytoplasmic ionized calcium concentration is unknown. We studied this problem by loading gel-filtered platelets with either quin2 or aequorin and stimulating them with epinephrine, arachidonate, thrombin, the calcium ionophore A23187, l-oleoyl-2-acetyl glycerol, or adenosine diphosphate in media with or without extracellular calcium. In response to all of these agonists, aequorin indicated an increase in cytoplasmic calcium that accompanied or preceded platelet aggregation. In calcium-containing media, verapamil, nifedipine, and diltiazem inhibited these effects in a concentration-dependent fashion, except for those produced by thrombin and A23187. Removal of extracellular calcium with EGTA reduced the calcium response to arachidonate, adenosine diphosphate, and l-oleoyl-2-acetyl glycerol, and the calcium response and aggregation were further inhibited by the calcium antagonists. In general, strong inhibition of the aequorin cytoplasmic calcium signal by approximately 100 μM concentrations of nifedipine, verapamil, and diltiazem was correlated with inhibition of platelet aggregation, but high concentrations of the inhibitors were required. Since inhibition by the calcium antagonists of the cytoplasmic calcium response and aggregation exceeded the effect of simple removal of extracellular calcium, these drugs may affect internal redistribution of calcium in human platelets.
维拉帕米和其他钙通道阻滞剂与α1-和α2-肾上腺素能受体的相互作用。
影响因子：
20.1
作者：
Motulsky,HJ;Snavely,MD;Hughes,RJ;Insel,PA
通讯作者：
Insel,PA