Winocour P D, Kinlough-Rathbone R L, Mustard J F
Thromb Haemost. 1981 Jun 30;45(3):257-62.
We have examined whether inhibition by mepacrine or freeing of arachidonic acid from platelet phospholipids inhibits platelet aggregation to collagen, thrombin or ADP, and the release reaction induced by thrombin or collagen. Loss of arachidonic acid was monitored by measuring the amount of 14C feed from platelets prelabelled with 14C-arachidonic acid. Mepacrine inhibited 14C loss by more than 80% but did not inhibit thrombin-induced platelet aggregation and had a small effect on release. ADP-induced platelet aggregation did not cause 14C loss. Mepacrine inhibited ADP-induced platelet aggregation by inhibiting the association of fibrinogen with platelets during aggregation. The effect of mepacrine on fibrinogen binding could be considerably decreased by washing the platelets but the inhibition of 14C loss persisted. Platelets pretreated with mepacrine and then washed show restoration of aggregation to collagen. Thus, mepacrine has two effects; 1. it inhibits phospholipases, 2. it inhibits fibrinogen binding. Freeing of arachidonic acid is not necessary for platelet aggregation or the release reaction.
我们研究了米帕林的抑制作用或从血小板磷脂中释放花生四烯酸是否会抑制血小板对胶原、凝血酶或二磷酸腺苷（ADP）的聚集，以及凝血酶或胶原诱导的释放反应。通过测量预先用14C-花生四烯酸标记的血小板中14C的释放量来监测花生四烯酸的损失。米帕林抑制14C损失超过80%，但不抑制凝血酶诱导的血小板聚集，对释放有轻微影响。ADP诱导的血小板聚集不会导致14C损失。米帕林通过抑制聚集过程中纤维蛋白原与血小板的结合来抑制ADP诱导的血小板聚集。通过洗涤血小板，米帕林对纤维蛋白原结合的作用可大大降低，但对14C损失的抑制作用仍然存在。先用米帕林预处理然后洗涤的血小板显示对胶原的聚集恢复。因此，米帕林有两种作用：1. 它抑制磷脂酶；2. 它抑制纤维蛋白原结合。血小板聚集或释放反应并不需要释放花生四烯酸。
