Neuropeptide Y receptor type 2 (NPY2R)

The Neuropeptide Y receptor type 2 (NPY2R), commonly known as the Y2 receptor, is a G protein-coupled receptor that serves as a primary mediator for the anorectic effects of the hormone Peptide YY (PYY) (Source: UniProt, P49146). It is highly expressed in the arcuate nucleus of the hypothalamus, where it functions as a presynaptic inhibitory autoreceptor on Neuropeptide Y (NPY) neurons to suppress appetite and promote satiety (Source: PubMed, PMID: 12110893). While PYY also interacts with other members of the NPY receptor family, such as Y1 and Y5, its truncated form PYY(3-36) is highly selective for the Y2 subtype, making this receptor the focal point for metabolic research (Source: PubMed, PMID: 21951318). Beyond its central role in energy homeostasis, NPY2R is involved in regulating gastrointestinal motility, inhibiting intestinal secretion, and modulating neurotransmitter release in the peripheral nervous system (Source: NIH, StatPearls - Physiology, Appetite). In the context of disease, dysregulation of the PYY-NPY2R axis is strongly linked to obesity and metabolic syndrome, making it a high-priority target for weight-loss pharmacotherapies (Source: PubMed, PMID: 21951318). Therapeutic strategies primarily involve the development of long-acting PYY(3-36) analogs or small-molecule agonists to induce weight loss, though clinical utility is often limited by gastrointestinal side effects such as nausea (Source: PubChem, CID 118704230; PubMed, PMID: 19079354).

Other names

Y2 receptorPeptide YY receptor type 2NPY2-RPYY2 receptorNPY-Y2 receptor

Agonism of the presynaptic Y2 receptor in the arcuate nucleus of the hypothalamus inhibits the release of orexigenic Neuropeptide Y (NPY), thereby suppressing appetite and increasing satiety.