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. 1978 Nov;62(5):923–930. doi: 10.1172/JCI109220

Stimulation of Endothelial Cell Prostacyclin Production by Thrombin, Trypsin, and the Ionophore A 23187

Babette B Weksler 1, Christopher W Ley 1, Eric A Jaffe 1
PMCID: PMC371849  PMID: 361756

Abstract

Prostacyclin (PGI2) is an unstable prostaglandin which inhibits platelet aggregation and serotonin release and causes vasodilation. The PGI2 activity produced by monolayers of cultured human endothelial cells and fibroblasts was measured by the ability of their supernates to inhibit platelet aggregation in platelet-rich plasma, or to inhibit thrombin-induced [14C]serotonin release from aspirin-treated, washed platelet suspensions. Monolayers of cultured human endothelial cells, stimulated with sodium arachidonate, thrombin, the ionophore A 23187, or trypsin, secreted PGI2 into the supernatant medium. Monolayers of fibroblasts produced PGI2 activity only when stimulated by arachidonate. “Resting,” intact monolayers did not produce detectable PGI2, nor did monolayers treated with ADP or epinephrine. Production of PGI2 activity was abolished by treatment of the monolayers with indomethacin, tranylcypromine, or 15-hydroperoxy arachidonic acid. The PGI2 activity of the supernates was destroyed by boiling or acidification. Inhibition of thrombin with diisopropylfluoro-phosphate, and of trypsin with soybean trypsin inhibitor, abolished the stimulation of PGI2 production by these enzymes. Production of thrombin at a site of vascular injury could, by stimulating PGI2 synthesis by endothelial cells adjacent to the injured area, limit the number of platelets involved in the primary hemostatic response and help to localize thrombus formation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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