A metabolically stable apelin-17 analog decreases AVP-induced antidiuresis and improves hyponatremia.
Fiche publication
Date publication
janvier 2021
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BONNET Dominique
Tous les auteurs :
Flahault A, Girault-Sotias PE, Keck M, Alvear-Perez R, De Mota N, Estéoulle L, Ramanoudjame SM, Iturrioz X, Bonnet D, Llorens-Cortes C
Lien Pubmed
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.
Référence
Nat Commun. 2021 01 12;12(1):305