Enhancement of the endothelial production of prostacyclin by inhibitors of protein synthesis.
1. Pretreatment of bovine aortic endothelial cells with cycloheximide enhanced their capacity to release prostacyclin in response to adenosine 5'-triphosphate (ATP) and bradykinin. 2. The action of cycloheximide was time-dependent; it became detectable after a 1 h exposure to the cells and was maximal after 3 h. 3. Puromycin mimicked the effect of cycloheximide. For these two agents, the enhancement of prostacyclin release was obtained at concentrations producing a partial inhibition of protein synthesis. 4. Cycloheximide increased the mobilization of free arachidonic acid induced by ATP in bovine aortic endothelial cells. 5. In conclusion, the synthesis of new proteins is not involved in the stimulatory action of ATP and bradykinin on prostacyclin production by bovine aortic endothelial cells. Despite the short half-life of prostaglandin H synthase in endothelial cells, cycloheximide and puromycin enhanced the release of prostacyclin induced by agonists. Our data suggest that this release might be under the control of rapidly turning-over phospholipase inhibitory proteins.
Boeynaems
J M
JM
Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, Belgium.
Boutherin-Falson
O
O
Lagneau
C
C
Galand
N
N
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006207:Half-Life; D014176:Protein Biosynthesis; D011691:Puromycin / Q000494:pharmacology; D011863:Radioimmunoassay
D000963:Antimetabolites; D001095:Arachidonic Acids; D016718:Arachidonic Acid; D011691:Puromycin; D000255:Adenosine Triphosphate; D003513:Cycloheximide; D011464:Epoprostenol; D001920:Bradykinin