Adrenaline potentiates type 2B von Willebrand factor-induced activation ofhuman platelets by enhancing both the formation and action of thromboxanes

Von Willebrand factor (vWF) is a large plasma glycoprotein that mediates pl atelet adhesion at sites of vascular injury. We have previously reported th at the pathological type 2B (formerly named type IIB) variant of VWF promot es platelet activation through phospholipase A(2)-mediated release of arach idonic acid. The present report shows that adrenaline (1 muM) potentiates t ype 2B vWF-induced platelet aggregation, serotonin secretion, rise in cytos olic Ca2+ concentration, and pleckstrin phosphorylation, as well as thrombo xane B-2 production. The hormone also increases the partially inhibited rel ease of serotonin observed in platelets pretreated with the anti-PIIb-IIIa antibody LJCP8 but does remove the total inhibition on the secretion caused by the anti-GPIb antibody LJIB1. Adrenaline also increases type 2B vWF-eli cited tyrosine phosphorylation of proteins with apparent molecular masses o f 60 and 80 kDa. Furthermore, adrenaline potentiates the rise in cytosolic Ca2+ and the release of thromboxane BZ in platelets stimulated with arachid onic acid (2 muM) as well as the increase in Ca2+ induced by the thromboxan e mimetic U46619 (0.3 muM) Platelet pretreatment with yohimbine or 13-azapr ostanoic acid, which are antagonists of the alpha (2)-adrenergic and thromb oxane receptors, respectively, or with acetylsalicylate and indomethacin, b oth of which act as inhibitors of thromboxane formation, abolishes the pote ntiating effect of adrenaline. These observations lead to the conclusion th at the potentiating action of adrenaline on type 2B vWF-promoted platelet r esponses is due to an increase in both the formation and activating action of thromboxanes. (C) 2000 Elsevier Science Ltd. All rights reserved.