{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNeuropeptide B/W receptor 2 (NPBWR2), also known as GPR8, is a G protein-coupled receptor that is activated by the regulatory peptides neuropeptide B (NPB) and neuropeptide W (NPW). In mammalian studies, binding assays have demonstrated that while both NPB and NPW can stimulate the receptor, NPW typically activates NPBWR2 with high potency whereas NPB requires higher concentrations for activation. This differential ligand potency has been linked to diverse physiological responses in the central nervous system, including the modulation of feeding behavior and nociception, as well as the control of adrenal corticosteroid secretion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn further investigations, the role of NPBWR2 was extended to the regulation of endocrine functions. For instance, experiments on human adrenal zona fasciculata-reticularis (ZF/R) cells revealed that activation of the receptor by its ligands not only elevates intracellular cyclic AMP levels (and in some instances, inositol triphosphate) but also promotes cortisol production via distinct signaling cascades. These findings highlight the receptor’s involvement in endocrine secretagogue actions and suggest that its activation modulates stress-related and metabolic responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nComparative studies in nonmammalian species have further underscored the conserved function of NPBWR2. In chickens, for example, the receptor—highly homologous to its human counterpart—is predominantly expressed in brain and pituitary tissues. Functional assays demonstrated that its activation by a specific isoform of NPW (cNPW23) effectively inhibits the secretion of growth hormone and prolactin from cultured pituitary cells. This direct pituitary action emphasizes NPBWR2’s integral role as a mediator of neuroendocrine regulation across vertebrate species."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stéphane Brezillon, Vincent Lannoy, Jean-Denis Franssen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of natural ligands for the orphan G protein-coupled receptors GPR7 and GPR8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M206396200"}], "href": "https://doi.org/10.1074/jbc.M206396200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12401809"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12401809"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hirokazu Tanaka, Tetsuo Yoshida, Norimasa Miyamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0837789100"}], "href": "https://doi.org/10.1073/pnas.0837789100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12719537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12719537"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "G Mazzocchi, P Rebuffat, A Ziolkowska, et al. "}, {"type": "b", "children": [{"type": "t", "text": "G protein receptors 7 and 8 are expressed in human adrenocortical cells, and their endogenous ligands neuropeptides B and w enhance cortisol secretion by activating adenylate cyclase- and phospholipase C-dependent signaling cascades."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2004-2132"}], "href": "https://doi.org/10.1210/jc.2004-2132"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15797961"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15797961"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Guixian Bu, Dongliang Lin, Lin Cui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of Neuropeptide B (NPB), Neuropeptide W (NPW), and Their Receptors in Chickens: Evidence for NPW Being a Novel Inhibitor of Pituitary GH and Prolactin Secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2016-1141"}], "href": "https://doi.org/10.1210/en.2016-1141"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27399877"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27399877"}]}]}]}