Neuropeptide Y receptor type 1 (NPY1R) (NPY1R)

Neuropeptide Y receptor type 1 (NPY1R) is a G protein-coupled receptor (GPCR) belonging to the rhodopsin-like family that mediates the biological actions of Neuropeptide Y (NPY) and Peptide YY (PYY) [2, 4]. It is widely expressed in the central nervous system, particularly in the hypothalamus, where it acts as a potent stimulator of food intake and a regulator of energy balance [1, 12]. In the periphery, NPY1R is located on vascular smooth muscle cells and mediates significant vasoconstriction, playing a key role in blood pressure regulation and cardiovascular remodeling [3, 13]. Beyond metabolism and hemodynamics, NPY1R is involved in modulating anxiety, stress resilience, and immune cell function, specifically influencing T cell activation and cytokine release [5, 6]. Due to its diverse roles, NPY1R is a significant therapeutic target for obesity, hypertension, and anxiety disorders, although the development of selective small-molecule ligands has proven challenging [13, 15]. Clinical interest also extends to oncology, as NPY1R is overexpressed in various tumors, including breast and prostate cancers, where it may influence cell proliferation and serve as a diagnostic biomarker [7, 11].

Other names

NPY1-RNPYRNPYR1Neuropeptide Y receptor Y1

NPY1R primarily functions through the Gi/o protein-coupled signaling pathway, leading to the inhibition of adenylate cyclase and a subsequent decrease in intracellular cAMP levels. It also triggers the mobilization of intracellular calcium and activates the mitogen-activated protein kinase (MAPK) pathway. Drugs targeting NPY1R typically act as competitive antagonists to block the orexigenic and vasoconstrictive effects of endogenous NPY, or as agonists to exploit its anxiolytic properties [4, 7, 17, 18].