Neuropeptide Y Y1 receptor (Y1R)

The Neuropeptide Y Y1 receptor (Y1R) is a member of the class A G protein-coupled receptor (GPCR) family and primarily mediates the actions of neuropeptide Y (NPY), one of the most potent appetite stimulants in mammals[2][5][7]. Y1R is expressed in the central nervous system (CNS), adipose tissue, vascular smooth muscle, and various other tissues, where it regulates food intake, energy homeostasis, anxiety-like behavior, cell proliferation, and gut function[1][6]. Antagonists selective for Y1R have shown promise as anti-obesity therapies and for certain cancers due to Y1R's role in promoting cell proliferation and its high expression in some tumors[3][7][9]. However, clinical translation has been limited by pharmacokinetic challenges. Y1R also participates in central and peripheral neuropeptide signaling networks that influence metabolic, psychiatric, and gastrointestinal diseases. Its molecular structure and ligand selectivity have been elucidated using high-resolution crystallography and cryo-EM, enabling rational drug design efforts[1][7].

Other names

Neuropeptide Y receptor type 1NPY Y1 receptorY1 receptorNPY1R (gene/protein abbreviation)

Antagonists inhibit Y1R signaling to reduce appetite, body weight, and potentially tumor growth Agonists (including endogenous NPY) activate Y1R to stimulate appetite and promote neurogenesis Modulation of Y1R may impact stress, anxiety, and depression pathways through effects on neurogenesis and neurotransmitter release