Neuropeptide Y receptors Y1, Y2, Y4, and Y5 (Y1, Y2, Y4, Y5 Receptors)

Neuropeptide Y receptors Y1, Y2, Y4, and Y5 are members of the G protein-coupled receptor (GPCR) superfamily and are the principal receptors mediating the physiological actions of neuropeptide Y, peptide YY, and pancreatic polypeptide. Each receptor subtype displays distinct expression patterns and selectivity for endogenous and synthetic ligands. Y1 and Y5 are primarily involved in promoting appetite and energy storage, while Y2 modulates neurotransmitter release and inhibits feeding via presynaptic mechanisms. Y4 is highly selective for pancreatic polypeptide and has roles in gastrointestinal function and appetite regulation. All subtypes couple mainly to G_i/o proteins, resulting in reduced cAMP and modulation of ion channels, affecting diverse biological functions including appetite, anxiety, cardiovascular and immune regulation, and bone homeostasis. These receptors are being actively studied as therapeutic targets for obesity, metabolic syndrome, psychiatric, and oncological diseases, although significant challenges remain with selectivity, safety, and system-wide effects[1][2][3][4][5][6].

Other names

Y1 receptor (NPY1R)Y2 receptor (NPY2R)Y4 receptor (NPY4R)Y5 receptor (NPY5R)Neuropeptide Y receptor type 1, type 2, type 4, type 5NPY Y1NPY Y2NPY Y4NPY Y5

Agonists (e.g., neuropeptide Y, peptide YY, pancreatic polypeptide) activate the receptor and lead to G_i/o protein coupling, inhibiting adenylate cyclase, decreasing cAMP, modulating Ca2+ and K+ channels, and thereby regulating neuronal activity and secretion[3][4][5] - Antagonists block these pathways, with potential applications in conditions like obesity, anxiety, and cancer