Physiological role of an endoperoxide in human platelets: hemostatic defect due to platelet cyclo-oxygenase deficiency.

Abstract

The endoperoxide prostaglandin G2 (PGG2) induced platelet aggregation as well as the platelet release reaction (release of ADP and serotonin) when added to human platelet-rich plasma. Formation of a metabolite of PGG2 [8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid] and a lipoxygenase product [12L-hydroxy-5,8,10,14-eicosatetraenoic acid] accompanied the release reaction caused by aggregating agents such as collagen, ADP, epinephrine, and thrombin. Indomethacin inhibited the release reaction and PGG2 formation induced by these agents but had no effect on PGG2-induced release reaction. The aggregating effect of PGG2 was abolished by furosemide, which is a competitive inhibitor of ADP-induced primary aggregation. These data indicate that the aggregating effect of PGG2 is due to release of ADP and that PGG2 synthesis is required for induction of the release reaction by various aggregating agents.A subject with a hemostatic defect due to abnormal release mechanism [decreased aggregation with epinephrine (second wave) and collagen and normal platelet ADP] had a deficiency of the cyclo-oxygenase that catalyzes formation of PGG2. Normal aggregation and release reaction were obtained with added PGG2.It is concluded that the endoperoxide (PGG2) is essential in normal hemostasis because of its role in initiating the release reaction required for aggregation by collagen and the second wave of aggregation caused by, e.g., ADP.

Enhancement of collagen‐induced phosphoinositide turnover by thromboxane A2 analogue through Ca2+ mobilization in human platelets

“…These reactions induced by collagen are inhibited by indomethacin or aspirin which are known to inhibit collagen-induced generation of PGG2, PGH2 and TXA2 [2,3]. These arachidonic acid metabolites have been shown to induce secretion and aggregation [2,3].…”

“…These reactions induced by collagen are inhibited by indomethacin or aspirin which are known to inhibit collagen-induced generation of PGG2, PGH2 and TXA2 [2,3]. These arachidonic acid metabolites have been shown to induce secretion and aggregation [2,3]. Based on these observations, it has been suggested that PGH2 and TXA2 may play a role of crucial importance in the action of collagen [2- [4] have shown that PGH2 and its stable analogue U46619 induce phosphoinositide turnover to a small extent but counteract the inhibition by aspirin of collagen-induced phosphoinositide turnover.…”

On the Interrelationship of Prostaglandin Endoperoxide G2 and Cyclic Nucleotides in Platelet Function

“…The ability of prostaglandin G2 to induce aggregation was inhibited by furosemide which is a competitive inhibitor of ADPinduced primary aggregation [ 3 61. A physiological role for prostaglandin Gz as a common mediator for various releasing agents has been demonstrated, and a case with functional lack of the platelet cyclooxygenase has been studied [16,17].It has been proposed by Salzman that prostaglandin synthesis is a prerequisite for the decrease of CAMP in human platelets [18]. Miller and Gorman have reported that prostaglandin G2 antagonized the increase of CAMP in response to prostaglandin El [19].…”

“…The ability of prostaglandin G2 to induce aggregation was inhibited by furosemide which is a competitive inhibitor of ADPinduced primary aggregation [ 3 61. A physiological role for prostaglandin Gz as a common mediator for various releasing agents has been demonstrated, and a case with functional lack of the platelet cyclooxygenase has been studied [16,17].…”

Effects of vitamin E on the platelet aggregation induced by combined adenosine diphosphate and hydrogen peroxide.

“…The endoperoxide prostaglandin G 2 (PGG2) derived from arachidonic acid is very potent in inducing platelet aggregatio n (Malmsten et al 1975). Mickel and Horbar (1974) reported that the platelet aggregation resulting from exposure to peroxidized arachidonic acid was abolished by prior treatment of the lipid peroxide with tocopherol and butylated hydroxytoluene .…”