Adenosine 3': 5'-cyclic monophosphate induces regulated secretion of tissue-type plasminogen activator and von Willebrand factor from cultured human endothelial …
RJ Hegeman, ES van den Y… - Thrombosis and …, 1998 - thieme-connect.com
RJ Hegeman, ES van den Y, JJ Emeis
Thrombosis and haemostasis, 1998•thieme-connect.comThe 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] 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 …
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 sub-maximal 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.
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