Insulin-Relaxin Family Peptide Signaling and Receptors in Mouse Brain Membranes and Neuronal Cells

: Several orphan G‐protein‐coupled receptors (GPCRs), LGR7 and LGR8, GPCR135 and GPCR142, were recently identified as putative, native receptors for different relaxin‐family peptides, and their cell signaling mechanisms were elucidated in stably transfected cell lines. Anatomic studies have demonstrated that discrete populations of neurons in rat brain express relaxin and relaxin‐3 mRNA/peptide, relaxin and relaxin‐3 binding sites, and LGR7 and GPCR135 mRNAs. Thus, we began to assess the ability of relaxin‐family peptides to alter cAMP production in brain and the involvement of the different native receptors. In mouse cortical membranes, a fixed concentration of relaxin peptides (100 nM) inhibited forskolin‐induced cAMP production, but further studies in normal and receptor knockout mouse strains are required to assess the specificity of these effects. In addition, whole‐cell signaling mechanisms are being investigated in a mouse hypothalamic cell line, GT1‐7. Such studies will help to establish the actions of relaxin‐family peptides via their different GPCRs in different brain pathways.