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Gene Review

NPY1R  -  neuropeptide Y receptor Y1

Homo sapiens

Synonyms: NPY1-R, NPYR, NPYY1, Neuropeptide Y receptor type 1
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Disease relevance of NPY1R


Psychiatry related information on NPY1R

  • The significance of different NPY receptor subtypes controlling estrous and feeding behavior is highlighted by results on expression of Fos immunoreactivity (Fos-IR) elicited by either PYY-(3-36) or [Leu(31),Pro(34)]PYY at a dose of each that differentiated between the two behaviors [5].

High impact information on NPY1R

  • Given that mRNA for the cloned Y5 receptor is apparently restricted to the CNS, Angela Bischoff and Martin Michel discuss the possible existence of additional NPY receptor subtypes with Y5-like recognition features and their presence in peripheral tissues [6].
  • The coupling of NPY receptors to various signal transduction mechanisms is also reviewed, including inhibition of adenylyl cyclase and stimulation or inhibition of increases in intracellular Ca2+, but a link between individual NPY receptor subtypes and specific signal transduction pathways has not been established [7].
  • Here we report the cloning by expression of a novel NPY receptor subtype from a rat hypothalamus cDNA library [8].
  • Expression of pS2, neuropeptide Y receptor Y1 and three novel clones was induced by estradiol, indicating estrogen-responsiveness [9].
  • The expression of the neuropeptide Y receptor Y1 gene (NPY1R localized at 4q31.3-q32) and the human guanine nucleotide-binding regulatory protein Go-alpha (GNAO1 localized at 16q13) was significantly decreased in individuals with schizophrenia compared to unaffected family controls by microarray and real-time PCR [10].

Biological context of NPY1R

  • As in the type 1 NPY receptor (Y1 receptor) gene, the 5'-untranslated region of the Y2 receptor is interrupted by an intervening sequence ( approximately 4.5 kb) [11].
  • To further our understanding of the genetic elements involved in the regulation of NPY receptor expression, we have cloned and characterized the human gene encoding the type 2 NPY receptor (Y2 receptor, HGMW-approved symbol NPY2R).2 The transcript spans 9 kb of genomic sequence and is encoded on two exons [11].
  • Specific links between individual NPY receptor subtype and a particular signal transduction pathway are not established [12].
  • Current drug discovery has produced a number of highly selective NPY receptor antagonists which have been used to establish the NPY Y(1) receptor subtype as the most critical in regulating short-term food intake [13].
  • However, it is too early to state with certainty whether a single subtype selective drug used alone or a combination of NPY receptor selective antagonists used in combination will be necessary to adequately influence appetite regulation [13].

Anatomical context of NPY1R


Associations of NPY1R with chemical compounds

  • Altered expression of NPY1R and C3 was also demonstrated at the protein level [18].
  • It is concluded that NPY releases intracellular Ca2+ from an inositol 1,4,5-trisphosphate-sensitive calcium pool, which is restored by external calcium, and that NPY receptor desensitization is protein kinase C independent [19].
  • CONCLUSIONS: Blockade of the NPY receptor may produce appetite-suppressing drugs [13].
  • ATP (10 micromol/l), a stable analogue ADP-beta S (3 micromol/l), and NE (1 micromol/l) had no effect on acetylcholine release. m-RNA for the NPY-receptor subtypes Y(1), Y(2), Y(4), Y(5), and y(6) was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) [20].
  • Our results demonstrate that (1) NPY modulates microvascular hemodynamics by changes in arteriolar diameter, (2) the NPY receptor on the hamster cheek pouch microvasculature is of the Y1 type, and (3) exogenous NPY-induced vasoconstriction is independent of the activity of endogenous norepinephrine [21].

Physical interactions of NPY1R

  • The regulation of NPY/NPY-R expression and function appears to be part of a complex system controlling multiple physiological functions, and its disruption might be relevant in the pathophysiology of disease states such as obesity [22].

Other interactions of NPY1R

  • Neuropeptide Y and its receptors NPY1R and NPY5R play a role in hippocampal learning and memory [23].
  • Novel treatments may emerge based upon VIP and NPY receptor antagonists if further work substantiates a role for gp120 in the vascular abnormalities of AIDS [24].
  • These values were compared to their binding affinities (IC50) for rat NPY receptor subtypes Y1, Y2, Y4 and Y5 in vitro [25].
  • Therefore, in the present study we investigated whether the anxiolytic action of (2S,3S,4S)-(carboxycyclopropyl)glycine (L-CCG-I), an mGlu2/3 receptor agonist, and (1S,3R,4S)-1-aminocyclopentane-1,3,4-tricarboxylic acid (ACPT-1), an mGluR4/6/7/8 receptor agonist, was mediated by a mechanism involving NPY receptor [26].
  • SNP, SIN-1, and SNAP decreased normal binding of NPY to the NPY1 receptor in SK-N-MC cells in a concentration-dependent manner [27].

Analytical, diagnostic and therapeutic context of NPY1R


  1. High expression of neuropeptide y receptors in tumors of the human adrenal gland and extra-adrenal paraganglia. Körner, M., Waser, B., Reubi, J.C. Clin. Cancer Res. (2004) [Pubmed]
  2. Functional effects of neuropeptide Y receptors on blood flow and nitric oxide levels in the human nose. Cervin, A., Onnerfält, J., Edvinsson, L., Grundemar, L. Am. J. Respir. Crit. Care Med. (1999) [Pubmed]
  3. Identification of high-potency neuropeptide Y analogues through systematic lactamization. Kirby, D.A., Britton, K.T., Aubert, M.L., Rivier, J.E. J. Med. Chem. (1997) [Pubmed]
  4. Involvement of G-protein alpha il subunits in activation of G-protein gated inward rectifying K+ channels (GIRK1) by human NPY1 receptors. Brown, N.A., McAllister, G., Weinberg, D., Milligan, G., Seabrook, G.R. Br. J. Pharmacol. (1995) [Pubmed]
  5. Neuropeptide Y inhibits estrous behavior and stimulates feeding via separate receptors in Syrian hamsters. Corp, E.S., Gréco, B., Powers, J.B., Marín Bivens, C.L., Wade, G.N. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2001) [Pubmed]
  6. Emerging functions for neuropeptide Y5 receptors. Bischoff, A., Michel, M.C. Trends Pharmacol. Sci. (1999) [Pubmed]
  7. Receptors for neuropeptide Y: multiple subtypes and multiple second messengers. Michel, M.C. Trends Pharmacol. Sci. (1991) [Pubmed]
  8. Identification of a novel hypothalamic neuropeptide Y receptor associated with feeding behavior. Hu, Y., Bloomquist, B.T., Cornfield, L.J., DeCarr, L.B., Flores-Riveros, J.R., Friedman, L., Jiang, P., Lewis-Higgins, L., Sadlowski, Y., Schaefer, J., Velazquez, N., McCaleb, M.L. J. Biol. Chem. (1996) [Pubmed]
  9. Differential screening and suppression subtractive hybridization identified genes differentially expressed in an estrogen receptor-positive breast carcinoma cell line. Kuang, W.W., Thompson, D.A., Hoch, R.V., Weigel, R.J. Nucleic Acids Res. (1998) [Pubmed]
  10. Microarray screening of lymphocyte gene expression differences in a multiplex schizophrenia pedigree. Vawter, M.P., Ferran, E., Galke, B., Cooper, K., Bunney, W.E., Byerley, W. Schizophr. Res. (2004) [Pubmed]
  11. Characterization of the human type 2 neuropeptide Y receptor gene (NPY2R) and localization to the chromosome 4q region containing the type 1 neuropeptide Y receptor gene. Ammar, D.A., Eadie, D.M., Wong, D.J., Ma, Y.Y., Kolakowski, L.F., Yang-Feng, T.L., Thompson, D.A. Genomics (1996) [Pubmed]
  12. Neuropeptide Y receptor subtypes. Wan, C.P., Lau, B.H. Life Sci. (1995) [Pubmed]
  13. Appetite suppression based on selective inhibition of NPY receptors. Chamorro, S., Della-Zuana, O., Fauchère, J.L., Félétou, M., Galizzi, J.P., Levens, N. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  14. NPY receptor subtype in the rabbit isolated ileum. Félétou, M., Nicolas, J.P., Rodriguez, M., Beauverger, P., Galizzi, J.P., Boutin, J.A., Duhault, J. Br. J. Pharmacol. (1999) [Pubmed]
  15. The effects of age on human venous responsiveness to neuropeptide Y. Lambert, M.L., Callow, I.D., Feng, Q.P., Arnold, J.M. British journal of clinical pharmacology. (1999) [Pubmed]
  16. The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y. Kask, A., Harro, J., von Hörsten, S., Redrobe, J.P., Dumont, Y., Quirion, R. Neuroscience and biobehavioral reviews. (2002) [Pubmed]
  17. alpha(2)-adrenoceptor and NPY receptor-mediated contractions of porcine isolated blood vessels: evidence for involvement of the vascular endothelium. Roberts, R.E., Kendall, D.A., Wilson, V.G. Br. J. Pharmacol. (1999) [Pubmed]
  18. Large-scale expression study of human mesial temporal lobe epilepsy: evidence for dysregulation of the neurotransmission and complement systems in the entorhinal cortex. Jamali, S., Bartolomei, F., Robaglia-Schlupp, A., Massacrier, A., Peragut, J.C., Régis, J., Dufour, H., Ravid, R., Roll, P., Pereira, S., Royer, B., Roeckel-Trevisiol, N., Fontaine, M., Guye, M., Boucraut, J., Chauvel, P., Cau, P., Szepetowski, P. Brain (2006) [Pubmed]
  19. Characterization of the neuropeptide Y-induced intracellular calcium release in human erythroleukemic cells. Daniels, A.J., Matthews, J.E., Humberto Viveros, O., Lazarowski, E.R. Mol. Pharmacol. (1992) [Pubmed]
  20. Neuropeptide Y inhibits acetylcholine release in human heart atrium by activation of Y2-receptors. Schwertfeger, E., Klein, T., Vonend, O., Oberhauser, V., Stegbauer, J., Rump, L.C. Naunyn Schmiedebergs Arch. Pharmacol. (2004) [Pubmed]
  21. Microcirculatory dynamics of neuropeptide Y. Kim, D., Durán, W.R., Kobayashi, I., Daniels, A.J., Durán, W.N. Microvasc. Res. (1994) [Pubmed]
  22. Hormonal control of the neuropeptide Y system. Magni, P. Curr. Protein Pept. Sci. (2003) [Pubmed]
  23. A case of autism with an interstitial deletion on 4q leading to hemizygosity for genes encoding for glutamine and glycine neurotransmitter receptor sub-units (AMPA 2, GLRA3, GLRB) and neuropeptide receptors NPY1R, NPY5R. Ramanathan, S., Woodroffe, A., Flodman, P.L., Mays, L.Z., Hanouni, M., Modahl, C.B., Steinberg-Epstein, R., Bocian, M.E., Spence, M.A., Smith, M. BMC Med. Genet. (2004) [Pubmed]
  24. HIV envelope protein gp120 induces neuropeptide Y receptor-mediated proliferation of vascular smooth muscle cells: relevance to AIDS cardiovascular pathogenesis. Kim, J., Ruff, M., Karwatowska-Prokopczuk, E., Hunt, L., Ji, H., Pert, C.B., Zukowska-Grojec, Z. Regul. Pept. (1998) [Pubmed]
  25. The pharmacology of neuropeptide Y (NPY) receptor-mediated feeding in rats characterizes better Y5 than Y1, but not Y2 or Y4 subtypes. Wyss, P., Stricker-Krongrad, A., Brunner, L., Miller, J., Crossthwaite, A., Whitebread, S., Criscione, L. Regul. Pept. (1998) [Pubmed]
  26. Anxiolytic action of group II and III metabotropic glutamate receptors agonists involves neuropeptide Y in the amygdala. Wierońska, J.M., Szewczyk, B., Pałucha, A., Brański, P., Zieba, B., Smiałowska, M. Pharmacological reports : PR. (2005) [Pubmed]
  27. Suppression of neuropeptide Y1 receptor function in SK-N-MC cells by nitric oxide. Dötsch, J., Hänze, J., Beste, O., Behrendt, J., Weber, W.M., Dittrich, K., Rascher, W. Am. J. Physiol. (1997) [Pubmed]
  28. Cloned human neuropeptide Y receptor couples to two different second messenger systems. Herzog, H., Hort, Y.J., Ball, H.J., Hayes, G., Shine, J., Selbie, L.A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  29. Interaction of neuropeptide Y and corticotropin-releasing factor signaling pathways in AR-5 amygdalar cells. Sheriff, S., Dautzenberg, F.M., Mulchahey, J.J., Pisarska, M., Hauger, R.L., Chance, W.T., Balasubramaniam, A., Kasckow, J.W. Peptides (2001) [Pubmed]
  30. Re-evaluation of receptor-ligand interactions of the human neuropeptide Y receptor Y1: a site-directed mutagenesis study. Sjödin, P., Holmberg, S.K., Akerberg, H., Berglund, M.M., Mohell, N., Larhammar, D. Biochem. J. (2006) [Pubmed]
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