Title
Adenosine 3':5'-cyclic monophosphate induces regulated secretion of tissue-type plasminogen activator and von Willebrand factor from cultured human endothelial cells
Author
Hegeman, R.J.
van den Eijnden-Schrauwen, Y.
Emeis, J.J.
Gaubius Instituut TNO
Publication year
1998
Abstract
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.
Subject
8-Bromo Cyclic Adenosine Monophosphate
Adenosine
Bucladesine
Calcium
Cells, Cultured
Cholera Toxin
Cyclic AMP
Endothelium, Vascular
Epoprostenol
Forskolin
Humans
Isoproterenol
Second Messenger Systems
Secretory Rate
Thrombin
Tissue Plasminogen Activator
von Willebrand Factor
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DOI
https://doi.org/10.1055/s-0037-1615077
TNO identifier
234425
ISSN
0340-6245
Source
Thrombosis and Haemostasis, 79 (4), 853-858
Document type
article