[1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors
Abstract
To date, there are no vasopressin (VP) agonists that exhibit a high affinity and selectivity for the VP V1b receptor with respect to the V1a, V2, and oxytocin receptors. In this study, we describe the synthesis and pharmacological properties of [1-deamino-4-cyclohexylalanine] arginine vasopressin (d[Cha4]AVP). Binding experiments performed on various membrane preparations revealed that d[Cha(4)]AVP exhibits a nanomolar affinity for V1b receptors from various mammalian species (rat, bovine, human). It exhibits high V1b/V1a and V1b/oxytocin selectivity for rat, human, and bovine receptors. Furthermore, it exhibits high V1b/V2 specificity for both bovine and human vasopressin receptors. Functional studies performed on biological models that naturally express V1b receptors indicate that d[Cha4]AVP is an agonist. Like VP, it stimulated basal and corticotropin-releasing factor-stimulated ACTH secretion and basal catecholamine release from rat anterior pituitary and bovine chromaffin cells, respectively. In vivo experiments performed in rat revealed that d[Cha4]AVP was able to stimulate both ACTH and corticosterone secretion and exhibits negligible vasopressor activity. It retains about 30% of the antidiuretic activity of VP. This long-sought selective VP V1b receptor ligand with nanomolar affinity will allow a better understanding of V1b-mediated VP physiological effects and is a promising new tool for V1b receptor structure-function studies.
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- Authors
- Derick, S., Cheng, L. L., Voirol, M. J., Stoev, S., Giacomini, M., Wo, N. C., Szeto, H. H., Ben Mimoun, M., Andres, M., Gaillard, R. C., Guillon, G., & Manning, M.
- Affiliations
- Inserm (FR)
- Medical College of Ohio (L.L.C., S.S., M.M.), Department of Biochemistry and Molecular Biology, Toledo, Ohio 43614
- Centre Hospitalier Universitaire Vaudois (CH)
- Cornell University (US)
- Institut National de la Santé et de la Recherche Médicale, Unité 469 (S.D., M.B.M., M.A., G.G.), 34094 Montpellier Cedex 05, France
- Corresponding author
- Guillon, G.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2002-12-01
- Volume
- 143
- Issue
- 12
- Pages
- 4655-4664
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2085319220
- Cited by
- 76
- References
- 44
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 4 · 2012: 4
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (GM25280, R01GM025280)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- vasopressin V1b receptor, receptor selectivity, V1a receptor, oxytocin receptor, V2 receptor, ACTH secretion, corticotropin-releasing factor, catecholamine release, anterior pituitary, chromaffin cells, corticosterone secretion, antidiuretic activity, receptor structure-function
- MeSH terms
- Adrenocorticotropic Hormone, Animals, Arginine Vasopressin, Catecholamines, Cattle, Cells, Cultured, Chromaffin System, Corticosterone, Corticotropin-Releasing Hormone, Diuresis, Female, Cricetinae, Humans, Pituitary Gland, Anterior, Transfection, Gene Expression, CHO Cells, Rats, Wistar, Receptors, Vasopressin, Receptors, Oxytocin, Rats
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