Adrenaline potentiates type 2B von Willebrand factor-induced activation of human platelets by enhancing both the formation and action of thromboxanes.
Von Willebrand factor (vWF) is a large plasma glycoprotein that mediates platelet adhesion at sites of vascular injury. We have previously reported that the pathological type 2B (formerly named type IIB) variant of vWF promotes platelet activation through phospholipase A(2)-mediated release of arachidonic acid. The present report shows that adrenaline (1 microM) potentiates type 2B vWF-induced platelet aggregation, serotonin secretion, rise in cytosolic Ca(2+) concentration, and pleckstrin phosphorylation, as well as thromboxane B(2) production. The hormone also increases the partially inhibited release of serotonin observed in platelets pretreated with the anti-GPIIb-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-elicited tyrosine phosphorylation of proteins with apparent molecular masses of 60 and 80 kDa. Furthermore, adrenaline potentiates the rise in cytosolic Ca(2+) and the release of thromboxane B(2) in platelets stimulated with arachidonic acid (2 microM) as well as the increase in Ca(2+) induced by the thromboxane mimetic U46619 (0.3 microM). Platelet pretreatment with yohimbine or 13-azaprostanoic acid, which are antagonists of the alpha(2)-adrenergic and thromboxane receptors, respectively, or with acetylsalicylate and indomethacin, both of which act as inhibitors of thromboxane formation, abolishes the potentiating effect of adrenaline. These observations lead to the conclusion that the potentiating action of adrenaline on type 2B vWF-promoted platelet responses is due to an increase in both the formation and activating action of thromboxanes.
Francesconi
M
M
Department of Biological Chemistry, C.N.R. Unit for the Study of Biomembranes, University of Padova, Italy.
Scapin
M
M
Casonato
A
A
Girolami
A
A
Deana
R
R
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008084:Lipoxygenase / Q000494:pharmacology; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology; D011466:Prostanoic Acids / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D013566:Sympathomimetics / Q000494:pharmacology; D013931:Thromboxanes / Q000096:biosynthesis / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology; D014841:von Willebrand Factor / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D010975:Platelet Aggregation Inhibitors; D011466:Prostanoic Acids; D013566:Sympathomimetics; D013931:Thromboxanes; D014662:Vasoconstrictor Agents; D014841:von Willebrand Factor; D016718:Arachidonic Acid; D015016:Yohimbine; D012701:Serotonin; D014443:Tyrosine; C022574:13-azaprostanoic acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D002118:Calcium; D004837:Epinephrine