Neuropeptide Y receptors in GtoPdb v.2023.1

Abstract

Neuropeptide Y (NPY) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Neuropeptide Y Receptors [158]) are activated by the endogenous peptides neuropeptide Y, neuropeptide Y-(3-36), peptide YY, PYY-(3-36) and pancreatic polypeptide (PP). The receptor originally identified as the Y3 receptor has been identified as the CXCR4 chemokine recepter (originally named LESTR, [139]). The y6 receptor is a functional gene product in mouse, absent in rat, but contains a frame-shift mutation in primates producing a truncated non-functional gene [84]. Three-dimensional structures have been determined for subtype active receptors Y₁, Y₂ and Y₄ [211, 114] and inactive antagonist bound Y₁ and Y₂ receptors [240, 210]. Many of the agonists exhibit differing degrees of selectivity dependent on the species examined. For example, the potency of PP is greater at the rat Y₄ receptor than at the human receptor [62]. In addition, many agonists lack selectivity for individual subtypes, but can exhibit comparable potency against pairs of NPY receptor subtypes, or have not been examined for activity at all subtypes. [¹²⁵I]-PYY or [¹²⁵I]-NPY can be used to label Y₁, Y₂, Y₅ and y₆ subtypes non-selectively, while [¹²⁵I][cPP(1-7), NPY(19-23), Ala³¹, Aib³², Gln³⁴]hPP may be used to label Y₅ receptors preferentially (note that cPP denotes chicken peptide sequence and hPP is the human sequence).