Nosál' R, Jancinová V, Danihelová E
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Thromb Res. 2000 Jun 1;98(5):411-21. doi: 10.1016/s0049-3848(00)00200-0.
Chloroquine inhibited human platelet aggregation in vitro both at receptor- and nonreceptor-operated stimuli. The inhibition was dose-dependent, recorded on isolated platelets as well as in platelet-rich plasma, and followed the rank order of stimuli: adrenaline (second phase)>phorbol 12-myristate 13 acetate>adenosine diphosphate>adrenaline (first phase)>thrombin>calcium ionophore A23187. In thrombin-activated platelets, chloroquine decreased in a dose-dependent manner phospholipase A(2)-induced arachidonic acid liberation from membrane phospholipids, malondialdehyde formation (a marker of membrane phospholipid peroxidation), and thromboxane generation, considered the most potent autoaggregatory agent. Chloroquine only slightly altered the arachidonic acid cascade of platelets stimulated with A23187 and phorbol 12-myristate 13 acetate. Histamine formation and liberation induced with thrombin and A23187 were not affected by chloroquine. On the other hand, thrombin-stimulated serotonin secretion was significantly decreased with chloroquine in the concentration of 10 micromol/L. This indicated that chloroquine might interfere with stimulated secretion from platelets. The results suggest that chloroquine inhibited activated platelets: first, intracellularly; second, in a close relationship to the intraplatelet Ca(2+) mobile pool; and third, most probably at the site of platelet phospholipase A(2) activation.
氯喹在体外对受体介导和非受体介导的刺激均能抑制人血小板聚集。这种抑制呈剂量依赖性，在分离的血小板以及富血小板血浆中均有记录，且遵循刺激因素的强度顺序：肾上腺素（第二相）>佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯>二磷酸腺苷>肾上腺素（第一相）>凝血酶>钙离子载体A23187。在凝血酶激活的血小板中，氯喹以剂量依赖性方式降低磷脂酶A₂诱导的膜磷脂花生四烯酸释放、丙二醛形成（膜磷脂过氧化的标志物）以及血栓素生成，血栓素被认为是最有效的自聚集剂。氯喹仅轻微改变由A23187和佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯刺激的血小板的花生四烯酸级联反应。凝血酶和A23187诱导的组胺形成和释放不受氯喹影响。另一方面，10微摩尔/升浓度的氯喹可显著降低凝血酶刺激的血清素分泌。这表明氯喹可能干扰血小板的刺激分泌。结果提示，氯喹抑制活化血小板：首先是在细胞内；其次，与血小板内钙离子移动池密切相关；第三，最有可能作用于血小板磷脂酶A₂的激活位点。
