Adenosine 3':5'-cyclic monophosphate induces regulated secretion of tissue-type plasminogen activator and von Willebrand factor from cultured human endothelial cells
van den Eijnden-Schrauwen, Y.
Gaubius Instituut TNO
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 dibutyrpl-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.
8-Bromo Cyclic Adenosine Monophosphate
To reference this document use:
Second Messenger Systems
Tissue Plasminogen Activator
von Willebrand Factor
Thrombosis and Haemostasis, 79 (4), 853-858