Kowalski K A, McConnell L A, Sadoff D A, Leid R W
Am J Pathol. 1983 Oct;113(1):1-7.
Equine platelets, when treated with the anthelmintic drug diethylcarbamazine (DEC), gave a dose-dependent release of radiolabeled serotonin without concomitant aggregation. At levels of the drug that gave only minimal release of radiolabel, marked dose-dependent inhibition of platelet aggregation to three of four platelet agonists tested--adenosine diphosphate (ADP), collagen, and arachidonic acid--was observed. With ADP, inhibition was observed to be reversed by removal of DEC prior to agonist challenge. However, with collagen, inhibition was only partially reduced by prior removal of DEC; whereas with arachidonate the DEC inhibition appeared not to be reduced by removal of the drug. Thrombin-induced aggregation was not inhibited by DEC. DEC therefore has the heretofore unrecognized property of modulating platelet function to several platelet agonists as well as inducing the platelet release of serotonin. Our results would suggest a reversible membrane-drug interaction as the potential site of modulation for ADP and collagen, whereas an apparent irreversible inhibition is suggested for arachidonate-induced aggregation.
马血小板在用驱虫药二乙碳酰嗪（DEC）处理后，会出现放射性标记的血清素剂量依赖性释放，且无伴随的聚集现象。在药物水平仅导致放射性标记物微量释放时，观察到对所测试的四种血小板激动剂中的三种——二磷酸腺苷（ADP）、胶原蛋白和花生四烯酸——的血小板聚集有明显的剂量依赖性抑制作用。对于ADP，在激动剂激发前去除DEC可观察到抑制作用被逆转。然而，对于胶原蛋白，预先去除DEC只能部分减轻抑制作用；而对于花生四烯酸盐，去除药物后DEC的抑制作用似乎并未减弱。凝血酶诱导的聚集不受DEC抑制。因此，DEC具有此前未被认识到的特性，即调节血小板对多种血小板激动剂的功能，以及诱导血小板释放血清素。我们的结果表明，对于ADP和胶原蛋白，可逆的膜-药物相互作用可能是调节位点，而对于花生四烯酸盐诱导的聚集则提示存在明显的不可逆抑制作用。
