The antagonism of prostaglandins I2, E1 and D2 by prostaglandin E2 in human platelets

Effects of thromboxane synthetase inhibition on arachidonate metabolism and platelet behaviour.

“…Relatively high levels (100 ng/ml) of PGE2 potentiate aggregation (Westwick, 1976), with even higher concentrations (1-3 [tg/ml) required to inhibit 0 aggregation (Bruno et al, 1974;Westwick, 1976) (Miller & Gorman, 1979;°> _~Bonne et al, 1981). The reported antagonism by PGE2 of the anti-aggregatory effects of PGE2, PGI2 and PGD2 (Bonne et al, 1981) seems to result from o both selective antagonism at the PGE1/PGI2 receptor and non-selective antagonism of adenylate cyclase. The very high levels of TXA2 generated when platelets are activated by exogenous AA (Tables 1 and 2) will be replaced after thromboxane synthetase inhibition by comparable levels of endoperoxides.…”

LOW CONCENTRATIONS OF PROSTAGLANDIN E2 INHIBIT THE PROSTACYCLIN‐INDUCED ELEVATION OF CYCLIC ADENOSINE 3′,5′‐MONOPHOSPHATE IN ELICITED POPULATIONS OF RAT PERITONEAL MACROPHAGES

“…To our knowledge no specific receptor binding studies with prostaglandins on macrophages have been published. The two-fold mechanisms as suggested by Bonne et al (1981) could just as well be valid for macrophages, because we also find that at a concentration of PGE2 above that which causes apparently maximal interference with DDH-carbo-PGI2, the inhibition is not observed, Since at concentrations above 10-8 M, PGE2 itself elevates the cyclic AMP levels in elicited peritoneal macrophages (Bonta et al, 1981b), this effect of PGE2 might have masked the prostacyclinantagonistic activity, as measured by the same parameter (see: Table 2). …”

“…It has been reported that added PGE2 causes a decrease in the responsiveness of platelets to PGE1 and PGI2 (Bonne et al, 1981 1.4 x 10-9 2.8 x 10-9 5.6 x 10-9 1.2 x 10-8 1.4 x 10-9 2.8 x 10-9 5.6 x 10-9 PGE1 from its specific binding sites in platelets (Bonne et al, 1981). These authors also presented results which suggested that direct inhibition of adenylate cyclase, rather than occupancy of the receptor, might be the mechanism underlying the prostaglandin-antagonistic activity of PGE2.…”

“…PGI2 is a particularly well-known potent inhibitor of platelet aggregation and a stimulator of cyclic AMP elevation in platelets (Tateson, Moncada & Vane, 1977). However, exposure of platelets to PGE2 renders these cells rather unresponsive to PGI2, both in terms of anti-aggregation and elevation of cyclic AMP (Bonne, Martin, Watada & Regnault, 1981). We now show that PGE2, in concentrations lower than those required to increase cyclic AMP in elicited peritoneal macrophages, inhibits the responsiveness of these cells to PGI2 and to (±)-5E-13,14-didehydro-carbo-prostacyclin (DDH-carbo-PGI2), a synthetic analogue not liable to undergo rapid decomposition.…”

A specific prostaglandin E2 receptor and its role in modulating salivary secretion in the female tick, Amblyomma americanum (L.)

“…In addition, PGE2 exerts a powerful modulating effect on human platelets, depending on the concentration of PGE2. At low concentration, PGE2 antagonizes the antiaggregatory action of PGE1 and PGI2 (Bonne et al, 1981).…”