Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP
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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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Vasopressin is synthesized in the hypothalamus and transported to the posterior pituitary, where it is released into the bloodstream during dehydration to act via V2 receptors on the kidneys to produce water retention.
“Vasopressin is a neurohormone that is synthesized in the hypothalamus and transported to the posterior pituitary (Brownstein et al., 1980), where it is released into the bloodstream during dehydration to act via vasopressin V 2 receptors on the kidneys to produce water retention (Kaufmann et al., 2000).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Kaufmann et al., 2000
The Introduction (page unavailable) states that vasopressin activates V2 receptors in renal collecting ducts, causing water retention. It does not address release into the bloodstream during dehydration. The hypothalamus-to-posterior-pituitary portion is cited to Brownstein et al., not Kaufmann et al. (LLM, conf=0.87)
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- 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)
- PMC
- PMC314363
- 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
- bronze
- doi.org
- 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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