Platelet activating factor enhances receptor-operated Ca(++)-influx and subsequent prostacyclin synthesis in human endothelial cells.
Platelet activating factor (PAF) primes vascular actions of mediators such as histamine and stimulates human umbilical vein endothelial cells (HUVECs) to produce prostacyclin (PGI2), which is important for the regulation of vascular tone, perfusion and hemostasis. We demonstrate that pretreatment of HUVECs with PAF enhances thrombin- or histamine-induced rises of cytosolic free Ca(++)-concentration and subsequent Ca(++)-dependent PGI2-synthesis. Inhibition of Ca(++)-influx and PGI2-formation by SKF96365 (blocker of receptor-operated Ca(++)-channels) in PAF-treated cells indicates that the enhancement of PGI2-synthesis by PAF is due to sensitization of Ca(++)-entry. This suggests cooperative effects of PAF on activation processes induced by thrombin or histamine in HUVECs.
Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten University of Munich, Germany.
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C
Weber
H J
HJ
Kruse
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A
Sellmayer
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W
Erl
P C
PC
Weber
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D016257:Fura-2; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D010972:Platelet Activating Factor / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013917:Thrombin / Q000494:pharmacology; D014471:Umbilical Veins
D007093:Imidazoles; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D015121:6-Ketoprostaglandin F1 alpha; D006632:Histamine; D011464:Epoprostenol; D013917:Thrombin; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium; D016257:Fura-2