Identification of binding sites with differing affinity and potency for relaxin analogues on LGR7 and LGR8 receptors.
This study defines the pharmacologic characteristics of LGR7 and LGR8, the receptors for H2 relaxin and INSL3 respectively, and determines the relative activity of relaxin-related peptides. We show, for the first time, the availability of two binding sites at LGR8 and confirm the presence of two sites at LGR7. Relaxin-related peptides had differing rank orders of affinity and potency at LGR7 and LGR8, but chimeric receptors were highly similar to their ectodomain-origin native receptors. The high-affinity site on the ectodomain coupled efficiently to cAMP production, whereas the low-affinity site in the transmembrane region coupled with decreased efficiency.
Halls
Michelle L
ML
Department of Pharmacology, PO Box 13E, Monash University, Clayton, Victoria 3800, Australia.
Bathgate
Ross A
RA
Sudo
Satoko
S
Kumagai
Jin
J
Bond
Courtney P
CP
Summers
Roger J
RJ
D000818:Animals; D001665:Binding Sites; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008024:Ligands; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D012065:Relaxin / Q000031:analogs & derivatives* / Q000378:metabolism*
D007328:Insulin; C084797:Leydig insulin-like protein; D008024:Ligands; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C504789:Rxfp1 protein, rat; C033395:relaxin receptors; D012065:Relaxin; D000242:Cyclic AMP