Activating the apelin receptor with LIT01-196, a metabolically stable apelin analog, reverses AVP-induced antidiuresis and hyponatremia - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2021

Activating the apelin receptor with LIT01-196, a metabolically stable apelin analog, reverses AVP-induced antidiuresis and hyponatremia

Résumé

Abstract 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.
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hal-03285794 , version 1 (23-11-2021)

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Adrien Flahault, Pierre-Emmanuel Girault-Sotias, Mathilde Keck, Rodrigo Alvear-Perez, Nadia de Mota, et al.. Activating the apelin receptor with LIT01-196, a metabolically stable apelin analog, reverses AVP-induced antidiuresis and hyponatremia. Nature Communications, 2021, 12 (1), ⟨10.1038/s41467-020-20560-y⟩. ⟨hal-03285794⟩
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