Vasopressin antagonists allow demonstration of a novel type of vasopressin receptor in the rat adenohypophysis

Details

Serval ID
serval:BIB_7080A5CE5439
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Vasopressin antagonists allow demonstration of a novel type of vasopressin receptor in the rat adenohypophysis
Journal
Molecular Pharmacology
Author(s)
Jard  S., Gaillard  R. C., Guillon  G., Marie  J., Schoenenberg  P., Muller  A. F., Manning  M., Sawyer  W. H.
ISSN
0026-895X (Print)
Publication state
Published
Issued date
08/1986
Volume
30
Number
2
Pages
171-7
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug
Abstract
The ligand specificity of rat adenohypophyseal vasopressin receptors was directly compared to that of peripheral receptors of the V1 and V2 types. For this purpose a series of 15 recently designed vasopressin antagonists was used. The affinities of these antagonists for rat adenohypophyseal membranes were deduced from the determination of the concentration-dependent inhibition of [3H]vasopressin binding. In parallel experiments the corticotropin (or anti-corticotropin)-releasing activities of the tested peptides were determined on freshly dispersed rat adenohypophyseal cells. All peptides tested which were found to be antagonists of the vasopressor and antidiuretic responses to vasopressin in vivo behaved as antagonists of vasopressin-induced corticotropin release. There was a close correlation between the relative affinities of the analogues tested for binding to adenohypophyseal membranes and their relative potencies in inhibiting vasopressin-induced corticotropin release, indicating that the detected vasopressin-binding sites are the receptors involved in the vasopressin effect on corticotropin secretion. No correlation could be demonstrated between anti-corticotropin-releasing activities and either anti-antidiuretic or antivasopressor potencies of the antagonists tested. A direct comparison of the ligand specificities of adenohypophyseal receptors on the one hand, and V1 (hepatic) and V2 (renal) receptors on the other hand, showed that most of the antagonists discriminated very efficiently between adenohypophyseal and either hepatic or renal receptors. The selectivity index reaches values as high as 260,000 for desGly(NH2)9 [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-D-O-ethyl-tyrosine, 4-valine] arginine vasopressin. It is concluded that adenohypophyseal receptors represent a novel type of vasopressin receptors. Based on the observation that adenohypophyseal receptors, like hepatic or vascular V1 receptors, do not appear to be coupled to adenylate cyclase, we propose that adenohypophyseal receptors could be designated as V1b receptors as opposed to the V1a receptors previously characterized on liver and blood vessels.
Keywords
Adrenocorticotropic Hormone/secretion Animals Cell Membrane/metabolism Diuresis/drug effects Female Kidney/metabolism Liver/metabolism Peptides/pharmacology Pituitary Gland, Anterior/drug effects/*metabolism Rats Rats, Inbred Strains Receptors, Angiotensin/*metabolism Receptors, Cell Surface/*metabolism Receptors, Vasopressin Structure-Activity Relationship Vasoconstriction/drug effects Vasopressins/*antagonists & inhibitors/metabolism/pharmacology
Pubmed
Web of science
Create date
15/02/2008 16:58
Last modification date
20/08/2019 14:29
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