Prostacyclin-dependent cyclic AMP formation in endothelial cells.
The effect of the stable prostacyclin (PGI2) mimetic iloprost on cyclic AMP levels was investigated in cultured porcine aortic endothelial cells. Iloprost (10(-10)-10(-5) mol/l) did not change cyclic AMP levels at passage 1 when endothelial cells were untreated but did so after inhibition of endogenous PGI2 formation by 48 or 72 h treatment with indomethacin or diclofenac (10(-5) mol/l). Iloprost increased cyclic AMP in a concentration-dependent manner and up to 6-fold above control when cells from passage 6 were used. In these cells, basal PGI2 generation was reduced to 20% of that at passage 1. Cyclic AMP stimulation by iloprost (10(-5) mol/l) in passage 6 cells was enhanced, reaching up to 11-fold the control level, when cells were cultured for 48 h in the presence of indomethacin or diclofenac (10(-5) mol/l). Cyclic AMP formation in LLC-PK1 cells, a kidney epithelial cell line without endogenous PGI2 biosynthesis, was markedly (25-fold above basal) stimulated by iloprost and unchanged by pretreatment with indomethacin and diclofenac. The data demonstrate that a continuous basal PGI2 generation occurs in porcine aortic endothelial cells that may be sufficient to completely desensitize PGI2-dependent adenylate cyclase activation, presumably at the receptor or GTP-binding protein level.
Schröder
H
H
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Federal Republic of Germany.
Schrör
K
K
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis*; D004008:Diclofenac / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000502:physiology*; D016285:Iloprost / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D013552:Swine
D004008:Diclofenac; D011464:Epoprostenol; D000242:Cyclic AMP; D016285:Iloprost; D007213:Indomethacin