Mechanism of the Antiplatelet Action of Dipyridamole in Whole Blood: Modulation of Adenosine Concentration and Activity
Mechanism of the Antiplatelet Action of Dipyridamole in Whole Blood: Modulation of Adenosine Concentration and Activity
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全血中双嘧达莫的抗血小板作用机制：腺苷浓度和活性的调节
DOI：
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发表时间：
1986
影响因子：
6.7
通讯作者：
J. Vermylen
中科院分区：
文献类型：
--
作者：
P. Gresele;J. Arnout;H. Deckmyn;J. Vermylen
双嘧达莫在低于血浆浓度时抑制全血中的血小板聚集。在血液中，负责提高疗效的血细胞是红细胞。利用阻抗聚集仪进行了一系列体外药理研究，以阐明潘生丁在全血中的作用机制。腺苷脱氨酶是一种分解腺苷的酶，它能逆转潘生丁的抑制作用。两种不同的腺苷受体拮抗剂5‘-脱氧-5’-甲硫基腺苷和茶碱也部分中和了血液中潘生丁的活性。Enproylline是一种几乎没有腺苷受体拮抗作用的磷酸二酯酶抑制剂，它能增强潘生丁对血小板聚集的抑制作用。单纯的腺苷摄取抑制剂(RE 102 BS)与单纯的磷酸二酯酶抑制剂(MX-MB 82或恩普罗林)联合使用，可获得与双嘧达莫相似的抑制作用。在预孵化过程中将血液与双嘧达莫混合会增加抑制程度。降低红细胞压积会略微降低疗效。虽然我们没有对腺苷水平进行直接测量，但我们的药理研究结果清楚地表明，双嘧达莫通过阻断微创伤后红细胞释放的前体形成的腺苷的再摄取来抑制全血中的血小板聚集。其轻微的磷酸二酯酶抑制作用增强了腺苷对血小板的影响。
Summary Dipyridamole inhibits platelet aggregation in whole blood at lower concentrations than in plasma. The blood cells responsible for increased effectiveness in blood are the erythrocytes. Using the impedance aggregometer we have carried out a series of pharmacological studies in vitro to elucidate the mechanism of action of dipyridamole in whole blood. Adenosine deaminase, an enzyme breaking down adenosine, reverses the inhibitory action of dipyridamole. Two different adenosine receptor antagonists, 5’-deoxy-5’-methylthioadenosine and theophylline, also partially neutralize the activity of dipyridamole in blood. Enprofylline, a phosphodiesterase inhibitor with almost no adenosine receptor antagonistic properties, potentiates the inhibition of platelet aggregation by dipyridamole. An inhibitory effect similar to that of dipyridamole can be obtained combining a pure adenosine uptake inhibitor (RE 102 BS) with a pure phosphodiesterase inhibitor (MX-MB 82 or enprofylline). Mixing the blood during preincubation with dipyridamole increases the degree of inhibition. Lowering the haematocrit slightly reduces the effectiveness. Although we did not carry out direct measurements of adenosine levels, the results of our pharmacological studies clearly show that dipyridamole inhibits platelet aggregation in whole blood by blocking the reuptake of adenosine formed from precursors released by red blood cells following microtrauma. Its slight phosphodiesterase inhibitory action potentiates the effects of adenosine on platelets.
5-甲硫腺苷和2,5-二脱氧腺苷通过不同机制阻断腺苷对ADP诱导的血小板聚集的抑制作用。
影响因子：
5.8
作者：
Agarwal,KC;ParksJr,RE
通讯作者：
ParksJr,RE
血细胞腺苷摄取和代谢在双嘧达莫、地拉西普和硝基苄硫肌苷的抗血小板作用中的作用。
影响因子：
5.8
作者：
Dawicki,DD;Agarwal,KC;ParksJr,RE
通讯作者：
ParksJr,RE