More information on this family may be found on the IUPHAR-DB family and introduction pages.
Neuropeptide Y (NPY) receptors (nomenclature agreed by NC-IUPHAR on Neuropeptide Y Receptors, [15]) are activated by the endogenous peptides NPY, NPY 3-36, peptide YY (PYY), 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, [13]). 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 [11]. Many of the agonists exhibit differing degrees of selectivity dependent on the species examined. For example, the relative potency of PP is greater at the rat Y4 receptor than at the human receptor [7]. 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.
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
|
||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
|
Brothers, SP; Wahlestedt, C. (2010) Therapeutic potential of neuropeptide Y (NPY) receptor ligands. EMBO Mol Med, 2 (11): 429-39. [PMID:20972986]
Lunniss, GE; Barnes, AA; Barton, N; Biagetti, M; Bianchi, F; Blowers, SM; Caberlotto, L; Emmons, A; Holmes, IP; Montanari, D; et al.. (2009) The identification and optimisation of novel and selective diamide neuropeptide Y Y2 receptor antagonists. Bioorg. Med. Chem. Lett., 19 (15): 4022-5. [PMID:19581086]
Michel, M. C., Beck-Sickinger, A. G., Cox, H., Doods, H. N., Herzog, H., Larhammar, D., Quirion, R., Schwartz, T. W. and Westfall, T. C. (1998) XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY and pancreatic polypeptide receptors. Pharmacol. Rev., 50: 143-150. [PMID:9549761]
Nguyen, AD; Herzog, H; Sainsbury, A. (2011) Neuropeptide Y and peptide YY: important regulators of energy metabolism. Curr Opin Endocrinol Diabetes Obes, 18 (1): 56-60. [PMID:21157324]
Tough, I. R., Holliday, N. D. and Cox, H. M. (2006) Y(4) receptors mediate the inhibitory responses of pancreatic polypeptide in human and mouse colon mucosa. J Pharmacol Exp Ther, 319: 20-30. [PMID:16807358]
1. Bard, J. A., Walker, M. W., Branchek, T. A. and Weinshank, R. L. (1995) Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY. J Biol Chem, 270: 26762-26765. [PMID:7592911]
2. Bonaventure, P; Nepomuceno, D; Mazur, C; Lord, B; Rudolph, DA; Jablonowski, JA; Carruthers, NI; Lovenberg, TW. (2004) Characterization of N-(1-Acetyl-2,3-dihydro-1H-indol-6-yl)-3-(3-cyano-phenyl)-N-[1-(2-cyclopentyl-ethyl)-piperidin-4yl]acrylamide (JNJ-5207787), a small molecule antagonist of the neuropeptide Y Y2 receptor. J. Pharmacol. Exp. Ther., 308 (3): 1130-7. [PMID:14617685]
3. Cabrele, C., Wieland, H. A., Koglin, N., Stidsen, C. and Beck-Sickinger, A. G. (2002) Ala31-Aib32: identification of the key motif for high affinity and selectivity of neuropeptide Y at the Y5-receptor. Biochemistry, 41: 8043-8049. [PMID:12069595]
4. Cox, HM; Tough, IR. (1995) Functional characterization of receptors with affinity for PYY, NPY, [Leu31,Pro34]NPY and PP in a human colonic epithelial cell line. Br. J. Pharmacol., 116 (6): 2673-8. [PMID:8590988]
5. Doods, H., Gaida, W., Wieland, H. A., Dollinger, H., Schnorrenberg, G., Esser, F., Engel, W., Eberlein, W. and Rudolf, K. (1999) BIIE0246: A selective and high affinity neuropeptide Y Y2 receptor antagonist. Eur. J. Pharmacol., 384: R3-R5. [PMID:10611450]
6. Dumont, Y; Thakur, M; Beck-Sickinger, A; Fournier, A; Quirion, R. (2004) Characterization of a new neuropeptide Y Y5 agonist radioligand: [125I][cPP(1-7), NPY(19-23), Ala31, Aib32, Gln34]hPP. Neuropeptides, 38 (4): 163-74. [PMID:15337369]
7. Eriksson, H; Berglund, MM; Holmberg, SK; Kahl, U; Gehlert, DR; Larhammar, D. (1998) The cloned guinea pig pancreatic polypeptide receptor Y4 resembles more the human Y4 than does the rat Y4. Regul. Pept., 75-76: 29-37. [PMID:9802391]
8. Gehlert, D. R., Beavers, L. S., Johnson, D., Gackenheimer, S. L., Schober, D. A. and Gadski, R. A. (1996) Expression cloning of a human brain neuropeptide Y Y2 receptor. Mol Pharmacol, 49: 224-228. [PMID:8632753]
9. Gerald, C., Walker, M. W., Criscione, L., Gustafson, E. L., Batzl-Hartmann, C., Smith, K. E., Vaysse, P., Durkin, M. M., Laz, T. M., Linemeyer, D. L., Schaffhauser, A. O., Whitebread, S., Hofbauer, K. G., Taber, R. I., Branchek, T. A. and Weinshank, R. L. (1996) A receptor subtype involved in neuropeptide-Y-induced food intake. Nature, 382: 168-171. [PMID:8700207]
10. Gerald, C., Walker, M. W., Vaysse, P. J., He, C., Branchek, T. A. and Weinshank, R. L. (1995) Expression cloning and pharmacological characterization of a human hippocampal neuropeptide Y/peptide YY Y2 receptor subtype. J Biol Chem, 270: 26758-26761. [PMID:7592910]
11. Gregor, P., Millham, M. L., Feng, Y., DeCarr, L. B., McCaleb, M. L. and Cornfield, L. J. (1996) Cloning and characterization of a novel receptor to pancreatic polypeptide, a member of the neuropeptide Y receptor family. FEBS Lett, 381: 58-62. [PMID:8641440]
12. Kanatani, A., Ishihara, A., Iwaasa, H., Nakamura, K., Okamoto, O., Hidaka, M., Ito, J., Fukuroda, T., MacNeil, D. J., Van der Ploeg, L. H., Ishii, Y., Okabe, T., Fukami, T. and Ihara, M. (2000) L-152,804: orally active and selective neuropeptide Y Y5 receptor antagonist. Biochem Biophys Res Commun, 272: 169-173. [PMID:10872822]
13. Loetscher, M., Geiser, T., O'Reilly, T., Zwahlen, R., Baggiolini, M. and Moser, B. (1994) Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem, 269: 232-237. [PMID:8276799]
14. Lundell, I., Blomqvist, A. G., Berglund, M. M., Schober, D. A., Johnson, D., Statnick, M. A., Gadski, R. A., Gehlert, D. R. and Larhammar, D. (1995) Cloning of a human receptor of the NPY receptor family with high affinity for pancreatic polypeptide and peptide YY. J Biol Chem, 270: 29123-29128. [PMID:7493937]
15. Michel, M. C., Beck-Sickinger, A. G., Cox, H., Doods, H. N., Herzog, H., Larhammar, D., Quirion, R., Schwartz, T. W. and Westfall, T. C. (1998) XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY and pancreatic polypeptide receptors. Pharmacol. Rev., 50: 143-150. [PMID:9549761]
16. Petitto, J. M., Huang, Z. and McCarthy, D. B. (1994) Molecular cloning of NPY-Y1 receptor cDNA from rat splenic lymphocytes: evidence of low levels of mRNA expression and [125I]NPY binding sites. J Neuroimmunol, 54: 81-86. [PMID:7929806]
17. Sjödin, P., Holmberg, S. K., Akerberg, H., Berglund, M. M., Mohell, N. and Larhammar, D. (2006) Re-evaluation of receptor-ligand interactions of the human neuropeptide Y receptor Y1: a site-directed mutagenesis study. Biochem J, 393: 161-169. [PMID:16097949]
18. Tough, I. R., Holliday, N. D. and Cox, H. M. (2006) Y(4) receptors mediate the inhibitory responses of pancreatic polypeptide in human and mouse colon mucosa. J Pharmacol Exp Ther, 319: 20-30. [PMID:16807358]
19. Wieland, H. A., Engel, W., Eberlein, W., Rudolf, K. and Doods, H. N. (1998) Subtype selectivity of the novel nonpeptide neuropeptide Y Y1 receptor antagonist BIBO 3304 and its effect on feeding in rodents. Br. J. Pharmacol., 125: 549-555. [PMID:9806339]
20. Yan, H., Yang, J., Marasco, J., Yamaguchi, K., Brenner, S., Collins, F. and Karbon, W. (1996) Cloning and functional expression of cDNAs encoding human and rat pancreatic polypeptide receptors. Proc Natl Acad Sci U S A, 93: 4661-4665. [PMID:8643460]
|
 @GuidetoPHARM  Like us on Facebook Privacy and Cookie Policy |
The Y1 agonists indicated are selective relative to Y2 receptors. BIBP3226 is selective relative to Y2, Y4 and Y5 receptors [9]. NPY-(13-36) is Y2 selective relative to Y1 and Y5 receptors. PYY-(3-36) is Y2 selective relative to Y1 receptors.