{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNeuropeptide Y receptor type 2 (NPY2R) is a G‐protein–coupled receptor that, upon activation by neuropeptide Y and related ligands, plays a pivotal role in the regulation of vascular tone and angiogenesis. Experimental studies in isolated human and animal blood vessels and endothelial cells have demonstrated that activation of NPY2R promotes endothelial cell migration, proliferation, and capillary tube formation—features that underpin ischemic angiogenesis. In addition, its expression in arterial and cerebral tissues, as well as in neoplastic lesions such as neuroblastomas and hemangiomas, supports a role for NPY2R in vascular remodeling and tumor growth processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNPY2R is also central to the regulation of energy balance, feeding behavior, and neuroprotection. In hypothalamic circuits, receptor activation by gut‐derived peptide YY mediates anorexic signals and influences satiety. Genetic association studies have implicated variations in the NPY2R gene or its regulatory regions in susceptibility to obesity, altered lipid profiles, and even differences in feeding maturation during the neonatal period. Moreover, evidence from neurodegenerative paradigms, including studies in Huntington disease, indicates that enhanced NPY2R expression or signaling may confer neuroprotection and modulate cognitive processes related to response selection. These findings collectively point to a multifaceted role of NPY2R in central metabolic regulation and stress‐related behaviors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, detailed structural and trafficking studies have further elucidated key regulatory motifs and dynamic properties of NPY2R. High‐resolution nuclear magnetic resonance and site–directed mutagenesis experiments have revealed that specific extracellular domains and a conserved C–terminal motif govern ligand binding, receptor activation, and subsequent internalization via both arrestin‐dependent and ‐independent mechanisms. Complementary biophysical approaches—including receptor reconstitution and fluorescence spectroscopy—have provided insight into receptor diffusion, dimerization, and membrane compartmentalization, thereby enhancing the pharmacological validation of NPY2R as a therapeutic target in diverse pathophysiological settings."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "36"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Helen M Cox, Iain R Tough "}, {"type": "b", "children": [{"type": "t", "text": "Neuropeptide Y, Y1, Y2 and Y4 receptors mediate Y agonist responses in isolated human colon mucosa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Pharmacol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjp.0704604"}], "href": "https://doi.org/10.1038/sj.bjp.0704604"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11906964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11906964"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rolf Uddman, Sebastian Möller, Torun Nilsson, et al. 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