Addonizio V P, Fisher C A, Strauss J F, Edmunds L H
Thromb Res. 1982 Nov 15;28(4):545-56. doi: 10.1016/0049-3848(82)90170-0.
We evaluated the ability of the calcium antagonist, verapamil, to alter human platelet function. With the concentrations tested (20 ng to 0.1 mg/ml of whole blood), verapamil inhibited epinephrine-induced aggregation and release of 14C-serotonin; produced a dose-dependent inhibition of 14C-serotonin uptake and prevented aggregation dependent release of thromboxane B2. The action of verapamil could be overcome by higher concentrations of both epinephrine and calcium. Furthermore, verapamil-induced inhibition could be reversed by gel-filtering platelets suggesting that verapamil's anti-platelet activity does not outlast its presence in plasma. Verapamil was relatively ineffective as an inhibitor of ADP-induced aggregation. As with epinephrine-induced platelet activation, the effects of verapamil on ADP-induced 14C-serotonin and thromboxane release correlated with its effects on secondary aggregation. Finally, verapamil failed to alter calcium ionophore-induced platelet aggregation. Thus, verapamil at the concentrations tested, appears to be functioning as a reversible, relatively specific inhibitor of epinephrine-induced platelet activation. Our findings suggest that the actions of verapamil in this regard are complex; there may be competitive inhibition of epinephrine binding as well as a blockade of epinephrine-induced calcium flux.
我们评估了钙拮抗剂维拉帕米改变人类血小板功能的能力。在所测试的浓度下（全血浓度为20纳克至0.1毫克/毫升），维拉帕米抑制肾上腺素诱导的聚集以及14C-血清素的释放；对14C-血清素的摄取产生剂量依赖性抑制，并阻止血栓素B2的聚集依赖性释放。更高浓度的肾上腺素和钙可克服维拉帕米的作用。此外，通过凝胶过滤血小板可逆转维拉帕米诱导的抑制作用，这表明维拉帕米的抗血小板活性不会超过其在血浆中的存在时间。维拉帕米作为ADP诱导聚集的抑制剂相对无效。与肾上腺素诱导的血小板活化一样，维拉帕米对ADP诱导的14C-血清素和血栓素释放的影响与其对继发性聚集的影响相关。最后，维拉帕米未能改变钙离子载体诱导的血小板聚集。因此，在所测试的浓度下，维拉帕米似乎作为肾上腺素诱导的血小板活化的可逆、相对特异性抑制剂发挥作用。我们的研究结果表明，维拉帕米在这方面的作用是复杂的；可能存在对肾上腺素结合的竞争性抑制以及对肾上腺素诱导的钙通量的阻断。
