Thrombin pretreatment of human platelets impairs thromboxane A2 synthesis
from endogenous precursors in the presence of normal cyclooxygenase
activity
HJ Reimers, RE Scharf and RK Baker
Exposure of horse platelets to thrombin has been reported to cause nearly
complete inactivation of cyclooxygenase within 30 sec. This contrasts with
the observation that human platelets, depleted of their granule
constituents by stimulation with thrombin, still aggregate in response to
arachidonic acid, a reaction presumably mediated by thromboxane A2 (TxA2)
formation. Because of this conflicting evidence, TxA2 formation was
measured by radioimmunoassay in washed human platelets depleted of their
alpha- and dense-storage granule constituents by prior stimulation with
thrombin. These platelets aggregated in response to adenosine diphosphate
(ADP), collagen, arachidonic acid, and thrombin, and formed TxA2. However,
collagen- and thrombin-induced TxA2 formation by these platelets was
reduced in comparison to control platelets that had not been depleted of
their storage granule constituents by prior thrombin stimulation. In
contrast, arachidonic acid-induced TxA2 formation was not significantly
different in thrombin-depleted and control platelets. These results
demonstrate that thrombin can induce degranulation of platelets without
concomitant inactivation of cyclooxygenase.
Volume 63,
Issue 4,
pp. 858-865,
04/01/1984
Copyright © 1984 by The American Society of Hematology
