title: Identification of binding sites with differing affinity and potency for relaxin analogues on LGR7 and LGR8 receptors.
abstract: 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.
authors.affiliation: Department of Pharmacology, PO Box 13E, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Halls
authors.forename: Ross A
authors.initials: RA
authors.lastname: Bathgate
authors.forename: Satoko
authors.initials: S
authors.lastname: Sudo
authors.forename: Jin
authors.initials: J
authors.lastname: Kumagai
authors.forename: Courtney P
authors.initials: CP
authors.lastname: Bond
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Summers
mesh_terms: 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*
chemical_list: 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