Salusin beta 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 beta activates the mouse mas-like G protein-coupled receptor, mMrgA1 with an EC(50) of about 300 nM. Salusin beta 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 beta does not activate corresponding human mas-like G protein-coupled receptors. Our results show that human salusin beta 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.
Wang
Zhiwei
Z
Department of Pharmacology, University of California, Irvine, CA 92697, USA.
Takahashi
Toshio
T
Saito
Yumiko
Y
Nagasaki
Hiroshi
H
Ly
Nga Kim
NK
Nothacker
Hans-Peter
HP
Reinscheid
Rainer K
RK
Yang
Jun
J
Chang
Jaw Kang
JK
Shichiri
Masayoshi
M
Civelli
Olivier
O
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; C470191:MrgA1 protein, mouse; D043562:Receptors, G-Protein-Coupled; C478739:TOR2A protein, human; D000251:Adenosine Triphosphatases