Stimulation of human endothelial cell prostacyclin synthesis by select leukotrienes.
Cultured endothelial cells from human umbilical cord labeled with [3H]20:4 release radiolabel when exposed to leukotrienes C or D (LTC or LTD). The major radiolabeled 20:4 metabolite recovered in the culture medium was prostacyclin. Both leukotrienes produced a dose-dependent synthesis of prostacyclin, with a maximal response at 10(-7) M leukotriene. LTC promoted a twofold greater response than did LTD at all concentrations tested (10(-9) to 10(-7) M). In contrast, no release of radiolabel above basal levels was evident with a challenge of LTE or LTB at the same concentrations. Endothelial cells metabolize approximately 40-50% of exogenously supplied LTC to LTD and LTE in 60 min. Levels of alpha-glutamyltranspeptidase (gamma-GTPase), the ectoenzyme reported to convert LTC or LTD, were detected in intact endothelial cells with the chromogenic substrate L-gamma-glutamyl-p-nitroanilide at levels sufficient to account for the observed rate of LTC metabolism. High concentrations of the gamma-GTPase inhibitors, glutathione and AT-125, blocked the metabolism of LTC by endothelium. These results suggest that degradation of leukotrienes by endothelium may be one mechanism for inactivation of these lipid mediators.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007975:Leukotriene B4 / Q000494:pharmacology; D017999:Leukotriene E4; D013189:SRS-A / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D014471:Umbilical Veins; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D001095:Arachidonic Acids; D013189:SRS-A; D007975:Leukotriene B4; D016718:Arachidonic Acid; D017999:Leukotriene E4; D006632:Histamine; D011464:Epoprostenol; D005723:gamma-Glutamyltransferase