[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
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
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 17:58
Last modification date
20/08/2019 14:39