Diminished platelet adenylate cyclase activation by prostaglandin D2 in
acute thrombosis
B Cooper
Prostaglandin D2 (PGD2) produced by platelets can inhibit aggregation via
activation of platelet adenylate cyclase. PGD2 activation of platelet
cyclase in platelet membrane fractions was studied in 20 consecutive
patients hospitalized with acute deep-vein thrombosis and/or pulmonary
embolism. In nine patients, PGD2-stimulated enzyme activity was decreased
at all concentrations of PGD2 studied. This altered enzyme sensitivity was
specific for PGD2 as basal enzyme activity, and prostaglandin E1,
prostaglandin I2, and sodium fluoride stimulated adenylate cyclase was
normal. The effect of PGD2 on platelet aggregation and 14C-serotonin
release was also studied in one patient where a four-fold higher
concentration of PGD2 was required to inhibit collagen-induced
14C-serotonin release. Binding studies using [3H]PGD2 as a radioligand
indicated that this patient's platelets bound 10 fmole PGD2/10(8) platelets
compared to 30 fmole/10(8) platelets in a normal control. Five patients had
follow-up studies between 2 and 7 mo after their acute thrombotic event,
and PGD2-stimulated adenylate cyclase activity returned towards normal in
four. Since PGD2 is synthesized in platelets at concentrations sufficient
to inhibit aggregation and activate adenylate cyclase, diminished platelet
sensitivity to this prostaglandin could result in "hyperactivity" and
contribute to the thrombosis observed in these patients.
Volume 54,
Issue 3,
pp. 684-693,
09/01/1979
Copyright © 1979 by The American Society of Hematology
