A metabolically stable apelin-17 analog decreases AVP-induced antidiuresis and improves hyponatremia.
Amino Acid Sequence
Animals
Apelin
/ administration & dosage
Apelin Receptors
/ metabolism
Arginine Vasopressin
/ adverse effects
Blood Glucose
/ metabolism
Blood Pressure
/ drug effects
Cell Line
Colforsin
/ pharmacology
Cyclic AMP
/ biosynthesis
Deamino Arginine Vasopressin
/ pharmacology
Disease Models, Animal
Diuresis
/ drug effects
Electrolytes
/ blood
Half-Life
Hyponatremia
/ blood
Kidney Tubules, Collecting
/ drug effects
Male
Mice
Models, Biological
Myocardial Contraction
/ drug effects
Peptides
/ chemistry
Phosphorylation
/ drug effects
Rats, Sprague-Dawley
Tolvaptan
/ pharmacology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 01 2021
12 01 2021
Historique:
received:
15
07
2019
accepted:
09
12
2020
entrez:
13
1
2021
pubmed:
14
1
2021
medline:
22
1
2021
Statut:
epublish
Résumé
Apelin and arginine-vasopressin (AVP) are conversely regulated by osmotic stimuli. We therefore hypothesized that activating the apelin receptor (apelin-R) with LIT01-196, a metabolically stable apelin-17 analog, may be beneficial for treating the Syndrome of Inappropriate Antidiuresis, in which AVP hypersecretion leads to hyponatremia. We show that LIT01-196, which behaves as a potent full agonist for the apelin-R, has an in vivo half-life of 156 minutes in the bloodstream after subcutaneous administration in control rats. In collecting ducts, LIT01-196 decreases dDAVP-induced cAMP production and apical cell surface expression of phosphorylated aquaporin 2 via AVP type 2 receptors, leading to an increase in aqueous diuresis. In a rat experimental model of AVP-induced hyponatremia, LIT01-196 subcutaneously administered blocks the antidiuretic effect of AVP and the AVP-induced increase in urinary osmolality and induces a progressive improvement of hyponatremia. Our data suggest that apelin-R activation constitutes an original approach for hyponatremia treatment.
Identifiants
pubmed: 33436646
doi: 10.1038/s41467-020-20560-y
pii: 10.1038/s41467-020-20560-y
pmc: PMC7804859
doi:
Substances chimiques
Apelin
0
Apelin Receptors
0
Blood Glucose
0
Electrolytes
0
Peptides
0
Arginine Vasopressin
113-79-1
Colforsin
1F7A44V6OU
Tolvaptan
21G72T1950
Cyclic AMP
E0399OZS9N
Deamino Arginine Vasopressin
ENR1LLB0FP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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