Overview
- Peptide (C)GMDEVKGEKQLGR, corresponding to amino acid residues 274 - 286 of mouse GPR173 (Accession Q6PI62). Intracellular, 3rd loop.
GPR173 Blocking Peptide (#BLP-GR093)
Western blot analysis of new born rat brain lysates (lanes 1 and 3) and mouse brain lysates (lanes 2 and 4):1-2. Anti-GPR173 Antibody (#AGR-093), (1:500).
3-4. Anti-GPR173 Antibody, preincubated with GPR173 Blocking Peptide (#BLP-GR093).
Western blot analysis of human SHSY-5Y neuroblastoma cell lysate (lanes 1 and 4), mouse BV-2 microglia cell lysate (lanes 2 and 5) and human HMC3 microglial cell line lysate (lanes 3 and 6):1-3. Anti-GPR173 Antibody (#AGR-093), (1:500).
4-6. Anti-GPR173 Antibody, preincubated with GPR173 Blocking Peptide (#BLP-GR093).
Expression of GPR173 in mouse hippocampusImmunohistochemical staining of perfusion-fixed frozen mouse brain sections with Anti-GPR173 Antibody (#AGR-093), (1:200), followed by goat anti-rabbit-AlexaFluor-488. A. Staining in the hippocampal CA3 region, showed GPR173 immunoreactivity (green) in cells of the pyramidal layer (arrows). B. Pre-incubation of the antibody with GPR173 Blocking Peptide (BLP-GR093), suppressed staining. Cell nuclei are stained with DAPI (blue). P = pyramidal layer.
Expression of GPR173 in rat parietal cortexImmunohistochemical staining of perfusion-fixed frozen rat brain sections with Anti-GPR173 Antibody (#AGR-093), (1:200), followed by goat anti-rabbit-AlexaFluor-488. A. GPR173 immunoreactivity (green) appears in neuronal profiles (arrows). B. Pre-incubation of the antibody with GPR173 Blocking Peptide (BLP-GR093), suppressed staining. Cell nuclei are stained with DAPI (blue).
- He, S. et al. (2023) J Neurosci, 43, 2305–2325.
- Mcilwraith, E.K. et al. (2019) Mol Cell Endocrinol, 499, 110606.
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GPR173, also referred to as SREB3 (Super Conserved Receptor Expressed in Brain 3), is a G-protein-coupled receptor (GPCR) belonging to the superfamily of Class A GPCRs. GPR173 is primarily localized to the cell membrane and is prominently expressed in the brain and gonads, particularly within hypothalamic kisspeptin and gonadotropin-releasing hormone (GnRH) neurons1,2.
The receptor is activated by Phoenixin (PNX), a neuropeptide involved in reproductive and hormonal regulation, as well as by GnRH-(1–5). PNX binding to GPR173 triggers the cAMP/PKA and MAPK signaling pathways, leading to increased expression of genes regulating reproduction, such as GnRH and Kiss1. On the other hand, GnRH-(1–5) activates GPR173 via the β-arrestin pathway, demonstrating its capacity for biased agonism2,3.
Beyond reproduction, GPR173 plays a significant role in modulating inflammatory and oxidative stress pathways. Inflammatory stimuli such as lipopolysaccharide (LPS) reduce GPR173 expression in astrocytes, microglia, and dental pulp cells. Activation of GPR173 by PNX-14 or PNX-20 has been shown to suppress pro-inflammatory cytokines and chemokines, as well as reduce oxidative stress by decreasing ROS production and increasing antioxidant enzymes such as superoxide dismutase (SOD)3,4,6,7.
GPR173 also attenuates LPS-induced endoplasmic reticulum (ER) stress by inhibiting the eIF-2α/ATF4/CHOP signaling pathway, preventing the activation of the NLRP3 inflammasome and the subsequent production of IL-1β and IL-18. These protective effects extend to reducing mitochondrial dysfunction, cell death, and infarct volume in neuroinflammatory and ischemic models3,4,7,8.
In vivo studies with siRNA knockdown of Gpr173 have shown significant disruptions in estrous cycling and reproductive hormone signaling, confirming its essential role in maintaining reproductive function. Dysregulation of GPR173 has also been linked to neuroinflammation, oxidative stress, and cell death, suggesting potential therapeutic implications for neurodegenerative diseases, stroke, and inflammatory disorders4,7,8.
Anti-GPR173 Antibody (#AGR-093) is a highly specific antibody directed against an epitope of the mouse protein. The antibody can be used in western blot and immunohistochemistry applications. It has been designed to recognize GPR173 from mouse, rat and human samples.
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