Salusin β is a surrogate ligand of the mas-like G protein-coupled receptor MrgA1

The mas-like G protein-coupled receptors form a subfamily of G protein-coupled receptors that includes variable member numbers across different species and that have been shown to bind a wide variety of ligands from peptides to amino acid derivatives. While screening a library of peptides against different orphan G protein-coupled receptors, we found that human salusin β activates the mouse mas-like G protein-coupled receptor, mMrgA1 with an EC₅₀ of about 300 nM. Salusin β is a bioactive peptide recently discovered through bioinformatics analysis which stimulates arginine-vasopressin release from rat pituitary and causes rapid and profound hypotension and bradycardia. However, when we further analyzed the generality of the mMrgA1 activation, we found that human salusin β does not activate corresponding human mas-like G protein-coupled receptors. Our results show that human salusin β is a surrogate ligand of the mouse MrgA1 and raises a cautionary flag for experiments that analyze the pharmacological profiles of mas-like G protein-coupled receptors from different species.