[1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors

Details

Serval ID
serval:BIB_407CD75C1567
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
[1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors
Journal
Endocrinology
Author(s)
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.
ISSN
0013-7227 (Print)
Publication state
Published
Issued date
12/2002
Volume
143
Number
12
Pages
4655-64
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Dec
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.
Keywords
Adrenocorticotropic Hormone/secretion Animals Arginine Vasopressin/analogs & derivatives/chemical synthesis/*metabolism/*pharmacology CHO Cells Catecholamines/secretion Cattle Cells, Cultured Chromaffin System/drug effects/secretion Corticosterone/secretion Corticotropin-Releasing Hormone/pharmacology Cricetinae Diuresis/drug effects Female Gene Expression Humans Pituitary Gland, Anterior/drug effects/secretion Rats Rats, Wistar Receptors, Oxytocin/metabolism Receptors, Vasopressin/*agonists/genetics/metabolism Transfection
Pubmed
Web of science
Open Access
Yes
Create date
15/02/2008 16:58
Last modification date
20/08/2019 13:39
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