Schlüter T, Bohnensack R
Institut für Biochemie, Medizinische Fakultät, Otto-von-Guericke-Universität, Magdeburg, Germany.
Biochem Pharmacol. 1999 May 15;57(10):1191-7. doi: 10.1016/s0006-2952(99)00011-8.
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.
内皮细胞能够合成血管性血友病因子（vWf）蛋白，该蛋白随后以组成型方式分泌或存储在特定的细胞分泌颗粒即魏尔-帕拉德小体中。这些细胞器中vWf的刺激分泌被认为是由导致细胞质钙浓度短暂升高的激动剂所诱导。血清素（5-羟色胺，5-HT）是活化血小板释放的一种局部递质物质，最近也被证明可诱导vWf的分泌。在用人脐静脉内皮细胞（HUVEC）进行的实验中，我们发现5-HT诱导的分泌在细胞钙水平无显著升高的情况下发生。5-HT 1(D)亚型特异性受体激动剂舒马曲坦也能诱导HUVEC中vWf的释放，且不会引起钙信号。用腺苷酸环化酶抑制剂MDL-12 A330刺激内皮细胞也会导致vWf的分泌。同时向HUVEC中添加亚最大浓度的组胺和5-HT可增强任一激动剂的作用。总之，这些结果表明在HUVEC中，5-HT诱导的vWf分泌是由环磷酸腺苷水平降低介导的，且与细胞质钙水平的变化无关。
