A role for intracellular histamine in collagen-induced platelet aggregation.
We previously demonstrated that newly formed intracellular histamine mediates platelet aggregation in response to phorbol-12-myristate-13-acetate (PMA). We now report further investigations of the role of histamine during physiological activation of platelets by collagen. Platelets stirred with collagen produced histamine; the rise in histamine precedes the onset of aggregation. The dose response for collagen stimulation of histamine synthesis and platelet aggregation is similar. Inhibitors of histidine decarboxylase (HDC) block both aggregation and histamine synthesis in parallel. Histamine production is not dependent on aggregation; both the intracellular histamine receptor antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE), and the cyclooxygenase inhibitors, aspirin and indomethacin, inhibit collagen-induced aggregation but not histamine synthesis. DPPE also inhibits collagen-induced serotonin secretion and thromboxane production. The effects of DPPE and HDC inhibitors are significantly reversed by the addition of histamine (0.1 to 10 mumol/L) to saponin-permeabilized platelets, though histamine alone has no pro-aggregatory effects. The results suggest that newly synthesized intracellular histamine has a role in collagen-induced platelet activation and that it may act to promote the generation of thromboxane and the secretion responses of platelet granules.
Saxena
S P
SP
Department of Pediatrics, Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
McNicol
A
A
Brandes
L J
LJ
Becker
A B
AB
Gerrard
J M
JM
D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D003094:Collagen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008661:Metabolism, Inborn Errors / Q000378:metabolism / Q000473:pathology; D008762:Methylhistidines / Q000494:pharmacology; D008854:Microscopy, Electron; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008762:Methylhistidines; D010714:Phosphatidylethanolamines; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; C046181:alpha-methylhistidine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D003094:Collagen; D011464:Epoprostenol; D013755:Tetradecanoylphorbol Acetate; D001241:Aspirin; D007213:Indomethacin