Protein kinase C-regulated production of prostacyclin by rat endothelium is increased in the presence of lipoxin A4.
Prostacyclin is generated by cultured rat endothelial cells. Compound blocking activity of protein kinase C and cyclic nucleotide-dependent protein kinases (H7) and compound blocking interaction between Ca2+ and calmodulin (W7) diminish generation of prostacyclin in rat endothelial cells. These compounds give a synergistic effect when they are introduced to the endothelial cell cultures simultaneously. Compound HA1004, an inhibitor of cAMP- and cGMP-dependent protein kinases has no effect on prostacyclin generation. Lipoxin A4, a potent direct stimulator of protein kinase C, rapidly induces prostacyclin generation in rat endothelium in a dose- and time-dependent fashion. Lipoxin A4-induced generation of prostacyclin can be inhibited by H7 and W7 but not by HA1004. Lipoxin B4 has no significant effect on prostacyclin generation in rat endothelium. In conclusion, our results demonstrate that generation of prostacyclin by rat endothelial cells is regulated via a pathway involving protein kinase C and Ca2+.
Leszczynski
D
D
Fourth Department of Surgery, University of Helsinki, Finland.
Ustinov
J
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects / Q000201:enzymology*; D011464:Epoprostenol / Q000096:biosynthesis*; D006706:Homeostasis; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D044045:Lipoxins; D009206:Myocardium / Q000201:enzymology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology
D002121:Calcium Channel Blockers; D006893:Hydroxyeicosatetraenoic Acids; D007546:Isoquinolines; D044045:Lipoxins; D010879:Piperazines; D013449:Sulfonamides; C040527:lipoxin A4; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011464:Epoprostenol; D011493:Protein Kinase C