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  • A metabolically stable apelin-17 analog decreases AVP-induced antidiuresis and improves hyponatremia.

A metabolically stable apelin-17 analog decreases AVP-induced antidiuresis and improves hyponatremia.

Nature communications (2021-01-14)
Adrien Flahault, Pierre-Emmanuel Girault-Sotias, Mathilde Keck, Rodrigo Alvear-Perez, Nadia De Mota, Lucie Estéoulle, Sridévi M Ramanoudjame, Xavier Iturrioz, Dominique Bonnet, Catherine Llorens-Cortes
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Apelin-17 trifluoroacetate salt, ≥95% (HPLC)