Aspirin does not inhibit adenosine diphosphate-induced platelet alpha-granule release.
The involvement of metabolites of arachidonic acid in platelet-dense granule secretion and secondary platelet-platelet interactions is well characterized. However, their role in heterotypic interactions dependent on alpha-granule secretion is less well understood. Using platelet-surface expression of P-selectin as a marker of alpha-granule secretion, we have shown that: (1) aspirin treatment of platelets at doses that block dense granule secretion does not inhibit alpha-granule secretion to adenosine diphosphate (ADP); (2) synergism between epinephrine and ADP in the induction of P-selectin expression is similarly unaffected by aspirin; and (3) the ability of P-selectin to mediate adhesion of activated platelets to monocytes and polymorphonuclear lymphocytes in whole blood is also unchanged by aspirin treatment. To further explore the mechanisms responsible for platelet alpha-granule secretion, we have shown that inhibition of Na+/H+ exchange by either acidification of the extracellular medium or amiloride treatment blocked ADP-induced P-selectin expression. In contrast, incubation with the platelet lipoxygenase inhibitor 5,8,11-eicosatrynoic acid, by itself and with aspirin, did not decrease ADP-induced P-selectin expression. We conclude that platelet alpha-granule secretion in response to ADP is dependent on intact Na+/H+ exchange but is independent of the lipoxygenase- and cyclooxygenase-dependent metabolites of arachidonic acid.
Rinder
C S
CS
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510.
Student
L A
LA
Bonan
J L
JL
Rinder
H M
HM
Smith
B R
BR
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000584:Amiloride / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000648:ultrastructure*; D002352:Carrier Proteins / Q000097:blood; D002462:Cell Membrane / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000502:physiology*; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D019007:P-Selectin; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D012701:Serotonin / Q000097:blood; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D016859:Lipoxygenase Inhibitors; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D017923:Sodium-Hydrogen Exchangers; D012701:Serotonin; D000244:Adenosine Diphosphate; D000584:Amiloride; D001241:Aspirin; D004837:Epinephrine