Prostaglandins and human platelet aggregation. Implications for the anti-aggregating activity of thromboxane-synthase inhibitors

Grazyna Rajtar, Chiara Cerletti, Maria Novella Castagnoli, Vittorio Bertelé, Giovanni de Gaetano

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Selective pharmacological blockade of thromboxane-synthase in human platelets by dazoxiben resulted in the reorientation of cyclic-endoperoxides towards PGE2, PGD2 and PGF2α. At concentrations which can be reached when thromboxane-synthase is inhibited, PGE2 (100-500 nM) exerted a marked, concentration-dependent pro-aggregatory effect. This required the formation of endogenous or the addition of exogenous endoperoxides and was prevented by PGD; or 13-aza-prostanoic acid, a selective antagonist of PGH2/TxA2 receptors. The anti-aggregating effect of PGD2 was evident at concentrations lower than those obtained in dazoxiben-treated platelets. It is proposed that in the absence of TxA2 generation, a combination of endoperoxides and PGE2 may result in normal aggregation. The latter may be inhibited by PGD2. No interference of PGF2α on platelet function could be shown.
Original languageItalian
Pages (from-to)307-310
Number of pages4
JournalBiochemical Pharmacology
Issue number3
Publication statusPublished - Feb 1 1985

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