Serotonin-induced secretion of von Willebrand factor from human umbilical vein endothelial cells via the cyclic AMP-signaling systems independent of increased cytoplasmic calcium concentration.
Endothelial cells are able to synthesize von Willebrand factor (vWf) protein, which is then either secreted in a constitutive way or stored within specific cellular secretory granules, the Weibel-Palade bodies. Stimulated secretion of vWf from these organelles is thought to be induced by agonists causing a transient increase in cytoplasmic calcium concentrations. Serotonin (5-hydroxytryptamine, 5-HT), a local transmitter substance released by activated platelets, has also recently been shown to induce the secretion of vWf. In experiments with human umbilical vein endothelial cells (HUVEC), we found that the 5-HT-induced secretion occurred without a significant increase in cellular calcium levels. The 5-HT 1(D) subtype-specific receptor agonist sumatriptan also induced the release of vWf without causing a calcium signal in HUVEC. Stimulation of endothelial cells with the adenylate cyclase inhibitor, MDL-12 A330, led to the secretion of vWf as well. Simultaneous addition of submaximal concentrations of histamine and 5-HT to HUVEC potentiated the effects of either agonist. Together, these results suggest that in HUVEC 5-HT-induced secretion of vWf is mediated by a decrease in cyclic AMP levels and is independent of changes in cytoplasmic calcium levels.
Institut für Biochemie, Medizinische Fakultät, Otto-von-Guericke-Universität, Magdeburg, Germany. thomas.schlueter@medizin.uni-magdeburg.de
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D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology; D020302:Weibel-Palade Bodies / Q000187:drug effects / Q000378:metabolism*; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism*
D000067956:Adenylyl Cyclase Inhibitors; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D014841:von Willebrand Factor; D012701:Serotonin; D006632:Histamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium