The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors
Abstract
The arginine vasopressin (AVP) type 2 receptor (V2R) is unique among AVP receptor subtypes in signaling through cAMP. Its key function is in the kidneys, facilitating the urine concentrating mechanism through the AVP/V2 type receptor/aquaporin 2 system in the medullary and cortical collecting ducts. Recent clinical and research observations strongly support the existence of an extrarenal V2R. The clinical importance of the extrarenal V2R spans widely from stimulation of coagulation factor in the endothelium to as yet untested potential therapeutic targets. These include V2R-regulated membranous fluid turnover in the inner ear, V2R-regulated mitogensis and apoptosis in certain tumor tissues, and numerous other cell types where the physiological role of V2Rs still requires further research. Here, we review current evidence on the physiological and pathophysiological functions of renal and extrarenal V2Rs. These functions of V2R are important, not only in rare diseases with loss or gain of function of V2R but also in relation to the recent use of nonpeptide V2R antagonists to treat hyponatremia and possibly retard the growth of cysts and development of renal failure in autosomal dominant polycystic kidney disease. The main functions of V2R in principal cells of the collecting duct are water, salt, and urea transport by modifying the trafficking of aquaporin 2, epithelial Na(+) channels, and urea transporters and vasodilation and stimulation of coagulation factor properties, mainly seen with pharmacological doses of 1-desamino-8-D-AVP. The AVPR2 gene is located on the X chromosome, in a region with high probability of escape from inactivation; this may lead to phenotypic sex differences, with females expressing higher levels of transcript than males.
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The behavioral effects of vasopressin are mediated primarily by V1aR and V1bR, while vasopressin acts on V2 to regulate fluid homeostasis in the kidney.
“The behavioral effects of AVP are mediated primarily by V1aR (or Avpr1a) and V1bR (16,37,38,49,68), while AVP acts on V2 to regulate fluid homeostasis in the kidney (69).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [69]
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Dumais, K. M., & Veenema, A. H. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2015.04.003 · Cited by 520 · see citing works
Measuring Oxytocin and Vasopressin: Bioassays, Immunoassays and Random Numbers
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“…and vasopressin act at four receptors: the oxytocin receptor (22); the V2 receptor, which accounts for the antidiuretic actions of vasopressin (23,24); the V1b receptor (25), which accounts for vasopressin effects on adrenocorticotrophin release; and the V1a receptor, which accounts for the…”
BackgroundOxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities
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Vasopressin in Vasodilatory Shock
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- Authors
- Juul, K. V., Bichet, D. G., Nielsen, S., & Nørgaard, J. P.
- Affiliations
- Ferring Pharmaceuticals (Denmark) (DK)
- Hôpital du Sacré-Cœur de Montréal (CA)
- Aarhus University (DK)
- Corresponding author
- Juul, Kristian Vinter
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2014-05-01
- Volume
- 306
- Issue
- 9
- Pages
- F931-F940
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- OpenAlex
- W2140057203
- Cited by
- 156
- References
- 140
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 6 · 2023: 11 · 2022: 12 · 2021: 18 · 2020: 15 · 2019: 14 · 2018: 11 · 2017: 16 · 2016: 12 · 2015: 18 · 2014: 3
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Renal Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Lundbeckfonden (R108-2012-10438)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Electrolyte and hormonal disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- vasopressin, V2 receptor, cAMP signaling, aquaporin-2, collecting duct, urine concentrating mechanism, urea transport, epithelial Na+ channel, vasodilation, hyponatremia, vasopressin V2 receptor antagonist, polycystic kidney disease, AVPR2 gene, X chromosome inactivation escape, sex differences
- MeSH terms
- Cyclic AMP, Animals, Female, Gene Expression Regulation, Genotype, Hormone Antagonists, Humans, Kidney, Male, Phenotype, Vasopressins, Water-Electrolyte Balance, Signal Transduction, Receptors, Vasopressin, Antidiuretic Hormone Receptor Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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