A role for intracellular histamine in collagen-induced platelet aggregation
SP Saxena, A McNicol, LJ Brandes, AB Becker and JM Gerrard
Department of Pediatrics, Manitoba Institute of Cell Biology, University of
Manitoba, Winnipeg, Canada.
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.
Volume 75,
Issue 2,
pp. 407-414,
01/15/1990
Copyright © 1990 by The American Society of Hematology
