Neuropeptide Y Receptor 2 Antibodies

The neuropeptide Y₂ (NPY₂) receptor is a class A G protein-coupled receptor that plays a key role in appetite regulation, energy homeostasis, and anxiety-related behaviors. Pharmacologically, it is activated by endogenous neuropeptide Y and peptide YY (PYY), with several experimental antagonists and agonists being investigated for potential treatment of obesity, metabolic disorders, and anxiety, though no NPY₂-selective drugs are widely approved for clinical use. Upon ligand binding, NPY₂ primarily couples to Gi/o proteins, leading to inhibition of adenylate cyclase, reduced intracellular cyclic AMP levels, and modulation of downstream signaling pathways affecting neuronal excitability and hormone secretion. Additional signaling involves MAP kinase pathways and regulation of ion channels, contributing to effects on feeding behavior and energy expenditure. NPY₂ is predominantly expressed in the hypothalamus, particularly in the arcuate nucleus where it functions as an autoreceptor to inhibit further NPY release, as well as in the brainstem and limbic system, regulating appetite and stress responses. Peripheral expression has also been reported in the gastrointestinal tract and pancreas, influencing gut motility and insulin secretion. Together, these pharmacological properties, signaling mechanisms, and expression patterns highlight NPY₂ as an important target in research on metabolic disorders and neuropsychiatric conditions. NPY2 receptor desensitization and internalization are regulated by phosphorylation of carboxyl-terminal serine351/serine354 (pS351/pS354-NPY2), serine354/threonine356 (pS354/pT356-NPY2) and serine351/serine354 (pS369/pS374-NPY2). This nomenclature refers to the human NPY2 receptor. This phosphorylation motif is highly conserved across species and very similar in mice and humans. For more information on NPY2 pharmacology please refer to the IUPHAR database. For further reading refer to: