|cAMP production Induced by Relaxin‑3 and Neutralization by Human Relaxin‑3 Antibody. Recombinant Human Relaxin‑3 (Catalog # 3107-RN) induces cAMP production in the THP‑1 human acute monocytic leukemia cell line in a dose-dependent manner (orange line), as measured by cAMP Parameter Assay Kit (Catalog # KGE002B). cAMP production elicited by Recombinant Human Relaxin‑3 (25 ng/mL) is neutralized (green line) by increasing concentrations of Mouse Anti-Human Relaxin‑3 Monoclonal Antibody (Catalog # MAB31071). The ND50 is typically 1-5 µg/mL.|
Human Relaxin-3 (H3 relaxin, INSL7) is one of seven relaxin-like peptides belonging to the insulin superfamily (1‑4). Unlike human relaxins 1 and 2, it does not play a role in reproduction but appears to be a neuropeptide involved in stress response in the brain stem (3‑5). The single-chain human Prorelaxin-3 shares 83% and 80% amino acid (aa) sequence identity with mouse and rat prorelaxin-3, respectively.The 142 aa Relaxin-3 pre-proprotein is processed to remove a 25 aa signal peptide and a connecting peptide (aa 53‑118). The resulting mature Relaxin-3 is a 5.5 kDa, 51 aa secreted heterodimer of A (aa 119‑142) and B (aa 26‑52) peptides connected by two intermolecular disulfide bonds (1). Mature human Relaxin-3 is 96%, 94%, and 92% aa identical to porcine, canine, and mouse Relaxin-3, respectively. This is much higher identity between species than that seen for other relaxins. Relaxin-3 is thus suggested to be the ancestral relaxin family member (2). Relaxin-3 is the only known ligand for the G-protein-coupled receptor GPCR135, designated RXFP3 (4, 6). In rodents, GPCR135 is expressed primarily in the supraoptic and paraventricular nucleus (6). This region has connections to the dorsal tegmental region of the pons (also called the nucleus incertus), where expression of Relaxin-3 is highest (5). Relaxin-3 also binds the more widely-expressed LGR7 (RXFP1) receptor, but with lower affinity than that of Relaxin-2 (1, 7). Although binding of Relaxin-3 to LGR7 increases intracellular cAMP, binding to GPCR135 inhibits cAMP accumulation, indicating coupling to Gi, Go or Gz by this receptor (1, 5). Relaxin-3 expression does not overlap well with its other receptor, GPCR142, which instead appears to be the primary receptor for INSL5 (3, 8).
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