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- W2888806403 abstract "PGE2 has a biphasic effect on platelet aggregation with low concentrations of the prostaglandin potentiating aggregation and high concentrations inhibiting it. In this investigation we have studied the interaction of PGE2 with agents that inhibit platelet aggregation through an effect on cAMP. The agents chosen raise the level of cAMP in platelets by different mechanisms: PGI2, PGD9 and adenosine combine with specific surface-located receptors and stimulate adenylate cyclase (AC) via a guanine nucleotide-binding protein (GNBP), forskolin stimulates AC directly, and AH-P 719 and DN 9693 inhibit cAMP phosphodiesterase (PDE). ADP-induced platelet aggregation was measured in platelet-rich plasma and cAMP was measured in platelets labelled with 3H-adenine. PGE2 alone potentiated platelet aggregation at concentrations from 10™8 -10™6 M and inhibited aggregation at 10™5M. PGE2 did not reduce cAMP levels at any concentration and increased cAMP levels at concentrations > 10™6 M, profcably by stimulating AC. PGI2 (10™9 -10™8 M), PGD2 (10™7 -5×10™6 M) and adenosine (8×l0™5-2×10™4 M) increased the level of cAMP in platelets and inhibited aggregation these changes were reversed by low concentrations of PGE2 (10™8-10™6M). Forskolin (5×10™6-2.5×10™5M), AH-P 719 (10™7-10™5M) and DN 9693 (5×10™6 -10™5M) increased the level of cAMP in platelets and inhibited aggregation. However, PGE2 did not reverse the inhibitory effects of these particular agents. In contrast, PGE2 potentiated the effects of the agents at all the concentrations of PGE2 that were tested (10™8-10™5M). The different results obtained with PGE2 in combination with agents that act via surface-located receptors compared with agents that stimulate AC directly or act through PDE, suggest that PGE2 may potentiate platelet aggregation by acting at a point between the platelet receptor and AC i.e. GNBP. PGE2 is one of the major prostaglandins synthesised by human microvascular endothelial cells and interstitial cells of the renal medulla. Since it reverses the inhibitory effects of some AC stimulators but adds to those of PDE inhibitors, the latter may have greater potential as anti-thrombotic agents in the micro-circulation and intra-renal circulation." @default.
- W2888806403 created "2018-09-07" @default.
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- W2888806403 date "1987-01-01" @default.
- W2888806403 modified "2023-09-23" @default.
- W2888806403 title "INTERACTIONS BETWEEn PGE2 AND INHIBITORS OF PLATELET AGGREGATION THAT ACT THROUGH cAMP" @default.
- W2888806403 doi "https://doi.org/10.1055/s-0038-1643582" @default.
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