Epinephrine--via activation of p38-MAPK--abolishes the effect of aspirin on platelet deposition to collagen.
The mechanism by which epinephrine enhances experimental thrombosis in the presence of aspirin is poorly understood. In this study, we set to explore, in aspirinised platelet-rich plasma (PRP), the effect of epinephrine (100 nmol/l) on platelet deposition to immobilised collagen and the subsequent involvement of several intracellular pathways. Under these experimental conditions, which allow platelet aggregation on top of the collagen-adherent platelets, epinephrine increased platelet deposition by 55-86%. This enhancement could be specifically prohibited by the alpha(2A)-adrenoceptor antagonist, atipamezole, the p38 mitogen-activated protein kinase (p38MAPK) inhibitor SB203580, and the cytosolic phospholipase A(2) (cPLA(2)) inhibitor, mepacrine. The effect of epinephrine coincided with increased phosphorylation of p38MAPK and cPLA(2) and with arachidonic acid (AA) release from platelet membrane. We conclude that epinephrine enhanced platelet deposition on collagen in aspirinised PRP via a mechanism dependent on both free AA in platelet cytosol (released by cPLA(2)) and p38MAPK.
Mustonen
P
P
Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland.
van Willigen
G
G
Lassila
R
R
D000328:Adult; D016824:Antigens, Human Platelet / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism / Q000502:physiology; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases
D016824:Antigens, Human Platelet; D024042:Collagen Type I; D004791:Enzyme Inhibitors; C083451:human platelet antigen 1b; D016718:Arachidonic Acid; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D001241:Aspirin; D004837:Epinephrine