PAF-acether-induced synthesis of prostacyclin by human endothelial cells.
Platelet activating factor, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF-acether) is a potent platelet-stimulating agent formed by most circulating cells. Added to cultured human endothelial cells, PAF-acether induced a dose-dependent synthesis of 6-keto-PGF1 alpha, the major stable metabolite of prostacyclin (PGI2), with a maximal effect at 100 nM, a concentration equivalent to that which aggregates human platelets. No release of von Willebrand factor (vWF) was noted under the same conditions. The poorly active PAF-acether analogue, methoxy-PAF failed to stimulate 6-keto-PFG1 alpha synthesis and the PAF-acether antagonists 48740 RP, BN 52021 and Ro 19-3704, prevented the stimulatory effect of PAF-acether. Methyl-carbamate-PAF, an equieffective analogue of PAF-acether on platelets, also stimulated 6-keto-PGF1 alpha production. After a first stimulation by PAF-acether or methyl-carbamate-PAF, no response was detected when endothelial cells were re-exposed to either agonist, indicating auto- and cross-desensitization as described for other cells. Since PAF-acether stimulated [3H]arachidonate release from pre-labelled endothelial cells, our results suggest that it stimulates phospholipase activity, which accounts for the increased PGI2 synthesis. The auto- and cross-desensitization between PAF-acether and methyl-carbamate-PAF, ineffectiveness of methoxy-PAF and inhibition by selective antagonists strongly suggest interaction with specific membrane receptors.
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D010743:Phospholipids / Q000096:biosynthesis; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011863:Radioimmunoassay; D014841:von Willebrand Factor / Q000378:metabolism
D001095:Arachidonic Acids; D010743:Phospholipids; D010972:Platelet Activating Factor; D014841:von Willebrand Factor; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol