RT Journal Article
SR Electronic
T1 Pharmacological Characterization of Relaxin-3/INSL7 Receptors GPCR135 and GPCR142 from Different Mammalian Species
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 83
OP 95
DO 10.1124/jpet.104.073486
VO 312
IS 1
A1 Jingcai Chen
A1 Chester Kuei
A1 Steven W. Sutton
A1 Pascal Bonaventure
A1 Diane Nepomuceno
A1 Elo Eriste
A1 Rannar Sillard
A1 Timothy W. Lovenberg
A1 Changlu Liu
YR 2005
UL http://jpet.aspetjournals.org/content/312/1/83.abstract
AB Relaxin-3 has recently been identified as a ligand for two structurally related G-protein-coupled receptors, human GPCR135 and GPCR142. This current study reports the characterization of mouse and rat GPCR135 as well as GPCR142 from mouse, monkey, cow, and pig at the molecular and pharmacological levels. Mouse and rat GPCR135 exhibit high homology (>85%) to the human GPCR135 and have very similar pharmacological properties to that of the human GPCR135. Human and mouse/rat relaxin-3 both bind to and activate mouse, rat, and human GPCR135 at high affinity with IC50 or EC50 values close to 0.5 nM. In contrast, the mouse GPCR142 is less well conserved (74% homology) with human GPCR142. The rat GPCR142 gene was found to be a pseudogene. We further cloned GPCR142 genes from monkey, cow, and pig and found that they are highly homologous (>84%) to human GPCR142. Pharmacological characterization of GPCR142 from different species demonstrated that relaxin-3 binds to GPCR142 from different species at high affinity (IC50 < 5 nM). However, relaxin-3 does not stimulate a Ca2+ response in cells coexpressing Gα16 and mouse GPCR142, whereas it does for cells expressing GPCR142 from other species tested. Our results suggest that GPCR142 may have a diminished role as a receptor for relaxin-3 in rodents, or perhaps GPCR142 functions as a receptor for another ligand in nonrodents. Boels and Schaller recently reported bradykinin as a ligand for GPCR142 (also known as GPR100). In this report, we demonstrate that bradykinin activates neither GPCR135 nor GPCR142, whereas relaxin-3 does. The American Society for Pharmacology and Experimental Therapeutics