Identification of relaxin-3/INSL7 as a ligand for GPCR142.
J Biol Chem. 2003
Pharmacological Characterization of Relaxin-3/INSL7 Receptors GPCR135 and GPCR142 from Different Mammalian Species.
Chen J, et al
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 Ca(2+) response in cells co-expressing Ga16 and mouse GPCR142 while 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 non-rodents. Boels and Schaller recently reported bradykinin as a ligand for GPCR142 (aka GPR100). In this report, we demonstrate that bradykinin activates neither GPCR135 nor GPCR142 whereas relaxin-3 does.