Autocrine regulation of endothelial exocytosis: von Willebrand factor release is induced by prostacyclin in cultured endothelial cells.
Vascular endothelial cells respond to external stimuli by altering the secretion of several bioactive molecules, including von Willebrand factor (vWf), prostacyclin (PGI2) and nitric oxide (NO). The release of all three molecules is regulated by a rise in cytosolic calcium ([Ca2+]i). In the present study we investigated whether cAMP-dependent signaling provides differential regulation of these effector systems by modulating the effect of [Ca2+]i in cultured human endothelial cells. The stable PGI2 analog iloprost, like other cAMP-raising agents (forskolin and adenosine), caused an acute dose-dependent increase in vWf release and potentiated the secretory response to thrombin. In contrast, iloprost, forskolin and adenosine failed to induce PGI2 release and inhibit thrombin-induced release. Our findings indicate cAMP-raising agents have opposite effects on [Ca2+]i-mediated vWf secretion and PGI2 release. PGI2 may potentiate vWf release and inhibit its own release in an autocrine manner.
Vischer
U M
UM
Department of Medicine, Geneva University Hospital, Switzerland. ulrich.vischer@medecine.unige.ch
Lang
U
U
Wollheim
C B
CB
D000241:Adenosine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism*
D014841:von Willebrand Factor; D009599:Nitroprusside; D005576:Colforsin; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D011464:Epoprostenol; D000242:Cyclic AMP; D013917:Thrombin; D016285:Iloprost; D000241:Adenosine