INSL5 is a high affinity specific agonist for GPCR142 (GPR100)

Abstract

Insulin-like peptide 5 (INSL5) is a peptide that belongs to the relaxin/insulin family, and its receptor has not been identified. In this report, we demonstrate that INSL5 is a specific agonist for GPCR142. Human INSL5 displaces the binding of 125I-relaxin-3 to GPCR142 with a high affinity (Ki = 1.5 nM). In a saturation binding assay, 125I-INSL5 binds GPCR142 with a Kd value of 2.5 nM. In functional guanosine (γ-thio)-triphosphate binding and cAMP accumulation assays, INSL5 potently activates GPCR142 with EC50 values of 1.3 and 1.2 nM, respectively. In addition, INSL5 stimulates Ca2+ mobilization in HEK293 cells expressing GPCR142 and Gα16. Overall, INSL5 behaves as an agonist for GPCR142 si..