Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP
Jocelyne E. Kaufmann, … , Walter Rosenthal, Ulrich M. Vischer
Jocelyne E. Kaufmann, … , Walter Rosenthal, Ulrich M. Vischer
Published January 1, 2000
Citation Information: J Clin Invest. 2000;106(1):107-116. https://doi.org/10.1172/JCI9516.
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Article

Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP

Abstract

Vasopressin and its analogue 1-deamino-8-D-arginine vasopressin (DDAVP) are known to raise plasma von Willebrand factor (vWF) levels. DDAVP is used as a hemostatic agent for the treatment of von Willebrand’s disease. However, its cellular mechanisms of action have not been elucidated. DDAVP, a specific agonist for the vasopressin V2 receptor (V2R), exerts its antidiuretic effect via a rise in cAMP in kidney collecting ducts. We tested the hypothesis that DDAVP induces vWF secretion by binding to V2R and activating cAMP-mediated signaling in endothelial cells. vWF secretion from human umbilical vein endothelial cells (HUVECs) can be mediated by cAMP, but DDAVP is ineffective, presumably due to the absence of V2R. We report that DDAVP stimulates vWF secretion in a cAMP-dependent manner in HUVECs after transfection of the V2R. In addition, vasopressin and DDAVP induce vWF secretion in human lung microvascular endothelial cells (HMVEC-L). These cells (but not HUVECs) express endogenous V2R, as shown by RT-PCR. Vasopressin-induced vWF secretion is mimicked by DDAVP and inhibited by the selective V2R antagonist SR121463B. It is mediated by cAMP, since it is inhibited by the protein kinase A inhibitor Rp-8CPT-cAMPS. These results indicate that vasopressin induces cAMP-mediated vWF secretion by a direct effect on endothelial cells. They also demonstrate functional expression of V2R in endothelial cells, and provide a cellular mechanism for the hemostatic effects of DDAVP.

Authors

Jocelyne E. Kaufmann, Alexander Oksche, Claes B. Wollheim, Gabriele Günther, Walter Rosenthal, Ulrich M. Vischer

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DDAVP-mediated vWF secretion from cells expressing V2R.EGFP. HUVECs were...
DDAVP-mediated vWF secretion from cells expressing V2R.EGFP. HUVECs were transfected with pV2R.EGFP or pA295.EGFP. Forty-eight hours later, EGFP-positive and -negative cells were sorted by FACS and seeded into 48-well plates. Seventy-two hours later they were incubated for 1 hour in KRBH containing 100 μM IBMX alone (open bars) or in the presence of either 0.1 μM DDAVP (shaded bars), or 10 μM forskolin (filled bars). Then, vWF in the media was measured by ELISA. The results are shown as a percentage of the vWF secreted in basal conditions (IBMX alone). The data are means ± SEM for six independent experiments. (AP < 0.01; BP < 0.001 by Student’s paired t test).