Adenosine 3':5'-cyclic monophosphate induces regulated secretion of tissue-type plasminogen activator and von Willebrand factor from cultured human endothelial cells.
The effect of compounds increasing intracellular adenosine 3':5'-cyclic monophosphate [cAMP]i levels (prostacyclin, isoproterenol, forskolin, cholera toxin), and of the cAMP analogs 8-bromo-cAMP and dibutyryl-cAMP, on the regulated secretion (acute release) of tissue-type plasminogen activator (tPA) and von Willebrand factor (vWF) was studied in cultured human umbilical vein endothelial cells (HUVEC). Prostacyclin, isoproterenol and forskolin, which increased [cAMP]i in HUVEC, and the cell-permeant cAMP analog 8-bromo-cAMP induced dose- and time-dependent secretion of tPA and vWF. The extent of vWF and tPA release correlated with [cAMP]i, and was increased by the phosphodiesterase inhibitor isobutylmethylxanthine. In contrast to thrombin, the cAMP-elevating agents did not increase the intracellular calcium concentration [Ca2+]i in HUVEC. At submaximal concentrations, the effects of thrombin and prostacyclin were additive. Our results show that an increase in [cAMP]i resulted in regulated secretion (acute release) of tPA and vWF from HUVEC, without the concomitant increase in [Ca2+]i which is, in HUVEC, essential for thrombin-induced regulated secretion to occur. cAMP-induced secretion represents a novel mechanism for causing regulated secretion of tPA and vWF from endothelial cells.
Hegeman
R J
RJ
Gaubius Laboratory TNO-PG, Leiden, The Netherlands.
van den Eijnden-Schrauwen
Y
Y
Emeis
J J
JJ
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
D014841:von Willebrand Factor; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C036038:8-bromoadenosine; D003994:Bucladesine; D002772:Cholera Toxin; D011464:Epoprostenol; D000242:Cyclic AMP; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D000241:Adenosine; D007545:Isoproterenol; D002118:Calcium