Cited by 275Platelet Disorders and TreatmentsCardiovascular, Neuropeptides, and Oxidative Stress ResearchBlood Coagulation and Thrombosis Mechanisms

The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.

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

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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.

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Metadata

Authors
Kaufmann, J. E., Oksche, A., Wollheim, C. B., Günther, G., Rosenthal, W., & Vischer, U. M.
Affiliations
  • University of Geneva (CH)
  • Leibniz-Forschungsinstitut für Molekulare Pharmakologie (DE)
Corresponding author
Kaufmann, Jocelyne E.
Venue
Journal of Clinical Investigation
Published
2000-07-01
Volume
106
Issue
1
Pages
107-116
ISSN
0021-9738 (ISSN-L)
OpenAlex
W2052753575
Cited by
275
References
47
Citations by year
2026: 5 · 2025: 9 · 2024: 6 · 2023: 14 · 2022: 11 · 2021: 12 · 2020: 12 · 2019: 9 · 2018: 15 · 2017: 7 · 2016: 13 · 2015: 12 · 2014: 13 · 2013: 15 · 2012: 8
FWCI
4.71
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • Fonds National de la Recherche Luxembourg
  • Helmut Horten Stiftung
Topics
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
vasopressin, von Willebrand factor secretion, V2 receptor, cAMP signaling, protein kinase A, endothelial cells, desmopressin, von Willebrand disease, hemostasis, lung microvascular endothelial cells
MeSH terms
Cyclic AMP, Arginine Vasopressin, Cells, Cultured, Deamino Arginine Vasopressin, Endothelium, Vascular, Humans, Lung, RNA, Messenger, von Willebrand Factor, Receptors, Vasopressin, Reverse Transcriptase Polymerase Chain Reaction

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