Effect of prostaglandin (PG) E1 and its initial metabolites on neutrophil-induced inhibition of human platelet aggregation.
We have investigated the effects of PGE1, 15-keto-PGE1, 15-keto-13,14-dihydro-PGE1 and 13,14-dihydro-PGE1 on inhibition of human platelet aggregation by rat peritoneal neutrophils (RPN) and human polymorphonuclear neutrophils (PMN). Both RPN and PMN are known to synthesize nitric oxide (NO). In the presence of a threshold concentration of RPN or PMN the inhibitory effects of PGE1 and 13,14-dihydro-PGE1 on thrombin- or collagen-induced platelet aggregation were significantly increased as compared to the absence of cells, while 15-keto-PGE1 and 15-keto-13,14-dihydro-PGE1 were inactive. Oxyhemoglobin (oxy-Hb) abolished the synergistic effect of RPN and either PGE1 or 13,14-dihydro-PGE1 on thrombin-induced platelet aggregation, but under the experimental conditions used had much less effect on inhibition of collagen-induced aggregation. Potentiation of the antiaggregatory effect of PGE1 and 13,14-dihydro-PGE1 by NO might contribute to the therapeutic efficacy of exogenous PGE1. This view is supported by the fact that plasma levels of PGE1 and its active metabolite in patients receiving infusions of PGE1 for treatment of peripheral arterial occlusive disease are in the order of magnitude acting synergistically with neutrophil-derived NO, while direct inhibition of platelet aggregation requires considerably higher concentrations of PGE1 and 13,14-dihydro-PGE1.
Pallapies
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Department of Pharmacology and Toxicology, Ruhr-University, Bochum, Germany.
Peskar
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BA
D000527:Alprostadil / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D003094:Collagen / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; C069881:13,14-dihydroprostaglandin E1; D009569:Nitric Oxide; D003094:Collagen; D013917:Thrombin; D000527:Alprostadil