Inhibition of Release of Arachidonic Acid by Monodansylcadaverine during Activation of Human Platelets by Collagen

抄録

Monodansylcadaverine (250μM), an inhibitor of transglutaminase, completely inhibited aggregation of human platelets induced by 2 μg/ml of collagen. Platelet responses necessary for aggregation (shape change, serotonin release, and phosphorylation of the 47, 000-Da protein) were also inhibited by this reagent. However, incorporation of [³H]putrescine into platelet proteins was very low and independent of the stimulation by collagen. It seems unlikely, therefore, that the transglutaminase reaction participates in platelet aggregation. Monodansylcadaverine inhibited the formation of thromboxane A₂ with a similar median inhibitory concentration (about 120μM) for aggregation. When platelets prelabeled with [¹⁴C]arachidonic acid were stimulated by collagen, the radioactivities in thromboxane B₂, hydroxyheptadecatrienoic acid, and hydroxyeicosatetraenoic acid increased. The increase was completely suppressed by the addition of monodansylcadaverine. Radioactivity in free arachidonic acid was very low throughout the experiments. From these results, it was concluded that monodansylcadaverine inhibited platelet aggregation by suppressing the release of arachidonic acid from phospholipids during platelet activation by collagen.