Neuropeptide Y receptor (NPYR)

Neuropeptide Y (NPY) receptors are a group of G protein-coupled receptors (GPCRs) that mediate the diverse physiological actions of Neuropeptide Y, one of the most abundant and widely distributed peptides in the mammalian nervous system [10, 15]. In humans, the functional subtypes include Y1, Y2, Y4, and Y5, which are primarily coupled to Gi/Go proteins and are expressed in both the central and peripheral nervous systems [2, 11]. These receptors play a central role in regulating energy homeostasis, with Y1 and Y5 subtypes acting as potent stimulators of food intake, while Y2 and Y4 are generally involved in satiety signaling [5, 15]. Beyond metabolism, NPY receptors modulate stress and anxiety responses, cardiovascular functions such as vasoconstriction and heart rate, and provide neuroprotective effects in conditions like epilepsy and neurodegeneration [1, 12, 18]. They are considered significant therapeutic targets for obesity, eating disorders, psychiatric conditions, and certain cancers like neuroblastoma, where they influence tumor cell proliferation and angiogenesis [13, 16]. Despite the development of numerous small-molecule modulators, achieving clinical efficacy remains challenging due to the complex interplay between receptor subtypes and the potential for off-target effects [4, 15].

Other names

NPY receptorY receptorNeuropeptide Y receptor familyNPY

Modulation of G protein-coupled receptor signaling (primarily Gi/Go) by agonists or antagonists to regulate downstream pathways such as adenylate cyclase inhibition, calcium mobilization, and MAPK activation, thereby influencing physiological processes like appetite, vascular tone, and neuronal excitability [2, 9, 13, 18].