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RW Colman, WR Figures, LM Scearce, AM Strimpler, FX Zhou and AK Rao
The relative roles of platelet autacoids such as adenosine diphosphate
(ADP), prostaglandin endoperoxides, and thromboxane A2 (TXA2) in
collagen-induced platelet activation are not fully understood. We
reexamined this relationship using the ADP affinity analogue, 5'-p-
fluorosulfonylbenzoyl adenosine (FSBA), which covalently modifies a
receptor for ADP on the platelet surface, thereby inhibiting ADP- induced
platelet activation. Collagen-induced shape change, aggregation, and
fibrinogen binding were each fully inhibited under conditions in which FSBA
is covalently incorporated and could not be overcome by raising the
collagen used to supramaximal concentrations. In contrast, TXA2 synthesis
stimulated by collagen under conditions that produced maximum aggregation
was only minimally inhibited by FSBA. Since covalent incorporation of FSBA
has been previously shown to specifically inhibit ADP-induced activation of
platelets, the present study supports the contention that ADP is required
for collagen-induced platelet activation. Under similar conditions,
indomethacin, an inhibitor of cyclooxygenase, inhibited collagen-induced
shape change, indicating that endoperoxides and/or TXA2 also play a role in
this response. Shape change induced by low concentrations (10 nmol/L) of
the stable prostaglandin endoperoxide, azo-PGH2, was also inhibited by
FSBA. These observations indicate a role for ADP in responses elicited by
low concentrations of endoperoxides. However, at higher concentrations of
azo-PGH2 (100 nmol/L), inhibition by FSBA could be overcome. Thus, the
effect of collagen apparently has an absolute requirement for ADP for
aggregation and fibrinogen binding and for both ADP and prostaglandins for
shape change. Aggregation and fibrinogen binding induced by prostaglandin
endoperoxides also required ADP as a mediator, but ADP is not absolutely
required at high endoperoxide concentration to induce shape change.
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| Copyright © 1986 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
