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Gene Review

NPY5R  -  neuropeptide Y receptor Y5

Homo sapiens

Synonyms: NPY-Y5 receptor, NPY5-R, NPYR5, NPYY5-R, Neuropeptide Y receptor type 5, ...
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Disease relevance of NPY5R

  • OBJECTIVE: To investigate whether the neuropeptide Y receptor 5 gene (NPY5R) is associated with obesity in humans [1].
  • We tested the hypothesis that blockade of the NPY5R will lead to weight loss in humans using MK-0557, a potent, highly selective, orally active NPY5R antagonist [2].
  • CONCLUSION: The results do not support a major role of the NPY Y5 receptor gene in the variability of body weight in children and adolescents [3].
  • Extended samples of these cohorts (160 obese children and adolescents; mean body mass index (BMI) 33.5 +/- 6.4 kg/m2, 128 underweight subjects; mean BMI 18.4 +/- 1.0 kg/m2 and 58 patients with AN; mean BMI 14.6 +/- 1.7 kg/m2) were screened to determine the frequencies of a detected mutation and a detected polymorphism in the NPY Y5 receptor gene [3].
  • In this issue of Cell Metabolism, identify a selective neuropeptide Y5 receptor antagonist that, as predicted from rodent studies, results in weight loss when administered to overweight and obese human subjects [4].

Psychiatry related information on NPY5R


High impact information on NPY5R

  • The extent to which selected peptides can inhibit adenylate cyclase through the Y5 receptor and stimulate food intake in rats correspond well [7].
  • 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 [8].
  • Conservation of expression of neuropeptide Y5 receptor between human and rat hypothalamus and limbic regions suggests an integral role in central neuroendocrine control [9].
  • We have performed a detailed analysis of Y5 expression in rat brain using in situ hybridization histochemistry with digoxygenin-labeled riboprobes and compared this to expression of Y5 in human brain regions. mRNA for the human Y5 receptor was highly expressed in human hypothalamic and thalamic nuclei [9].
  • 3) RT-PCR shows expression of Y1, Y2, Y4, and Y5 receptor mRNA by chromaffin cells; these receptors are functional, as various receptor specific agonists elicit an increase in intracellular calcium [10].

Chemical compound and disease context of NPY5R

  • CONCLUSION: Considering the importance of this gene in regulation of body weight, the association of these polymorphisms with extremes of BMI in Pima Indians indicates that NPY5R, or a locus nearby, may contribute to susceptibility to obesity in this population [1].

Biological context of NPY5R


Anatomical context of NPY5R


Associations of NPY5R with chemical compounds

  • DESIGN: The NPY5R gene was screened for polymorphisms by direct sequencing in two groups of Pima Indians, selected for extremes of body mass index (BMI) [1].
  • In contrast, NPY5 agonists, through the NPY5 receptor which is negatively coupled to the same pathway, counteract the alphaMSH-mediated effect on cyclic AMP level [5].
  • The structure-activity relationships are described and compound 2o (FR226928) showed the most potent affinity for Y5 receptor of all we prepared and was found to have higher potency and better selectivity for Y5 over Y1 receptor affinities when compared with the known lead compound 1 [17].
  • Neuropeptide Y lowers blood glucose in anaesthetized rats via a Y5 receptor subtype [18].
  • We evaluated the pharmacological profiles of FMS586 [3-(5,6,7,8-tetrahydro-9-isopropyl-carbazol-3-yl)-1-methyl-1-(2-pyridin-4-yl-ethyl)-urea hydrochloride], a novel tetrahydrocarbazole derivative as a neuropeptide Y (NPY) Y5 receptor antagonist [19].

Physical interactions of NPY5R

  • Receptor-binding experiments confirmed NPY binding of the Y1 receptor in the nanomolar range but gave no evidence for high expression levels of Y5 receptor subtypes on the cell surface [20].

Regulatory relationships of NPY5R


Other interactions of NPY5R

  • Spontaneous contractions of the rabbit isolated ileum were recorded and binding experiments were performed in cells expressing the human NPY Y1, Y2, Y4 or Y5 receptor subtype [14].
  • Neuropeptide Y and its receptors NPY1R and NPY5R play a role in hippocampal learning and memory [22].
  • Our data in vivo are inconsistent with findings that hPP, [Leu31 Pro34]-rNPY and [D-Trp32]-rNPY are full agonists at the rat cloned Y5 receptor [23].
  • The Y5 receptor mRNA is most abundant and most widely distributed (CA3 > DG approximately = CA2 approximately = CA1) [24].
  • Among 10 genes screened out, dopamine D3 receptor (DRD3) and neuropeptide Y Y5 receptor (NPYY5) genes were submitted to RT-PCR quantification and showed consistent results with microarray [25].

Analytical, diagnostic and therapeutic context of NPY5R


  1. Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians. Jenkinson, C.P., Cray, K., Walder, K., Herzog, H., Hanson, n.u.l.l., Ravussin, E. Int. J. Obes. Relat. Metab. Disord. (2000) [Pubmed]
  2. Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults. Erondu, N., Gantz, I., Musser, B., Suryawanshi, S., Mallick, M., Addy, C., Cote, J., Bray, G., Fujioka, K., Bays, H., Hollander, P., Sanabria-Boh??rquez, S.M., Eng, W., L??ngstr??m, B., Hargreaves, R.J., Burns, H.D., Kanatani, A., Fukami, T., Macneil, D.J., Gottesdiener, K.M., Amatruda, J.M., Kaufman, K.D., Heymsfield, S.B. Cell metabolism. (2006) [Pubmed]
  3. Screening for mutations in the neuropeptide Y Y5 receptor gene in cohorts belonging to different weight extremes. Rosenkranz, K., Hinney, A., Ziegler, A., von Prittwitz, S., Barth, N., Roth, H., Mayer, H., Siegfried, W., Lehmkuhl, G., Poustka, F., Schmidt, M., Schäfer, H., Remschmidt, H., Hebebrand, J. Int. J. Obes. Relat. Metab. Disord. (1998) [Pubmed]
  4. Treating obesity: Does antagonism of NPY fit the bill? Farooqi, S. Cell metabolism. (2006) [Pubmed]
  5. Functional characterization of human neuropeptide Y receptor subtype five specific antagonists using a luciferase reporter gene assay. Beauverger, P., Rodriguez, M., Nicolas, J.P., Audinot, V., Lamamy, V., Dromaint, S., Nagel, N., Macia, C., Léopold, O., Galizzi, J.P., Caignard, D.H., Aldana, I., Monge, A., Chomarat, P., Boutin, J.A. Cell. Signal. (2005) [Pubmed]
  6. The neuropeptide-Y Y5 receptor antagonist L-152,804 decreases alcohol self-administration in inbred alcohol-preferring (iP) rats. Schroeder, J.P., Overstreet, D.H., Hodge, C.W. Alcohol (2005) [Pubmed]
  7. A receptor subtype involved in neuropeptide-Y-induced food intake. 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., Weinshank, R.L. Nature (1996) [Pubmed]
  8. Emerging functions for neuropeptide Y5 receptors. Bischoff, A., Michel, M.C. Trends Pharmacol. Sci. (1999) [Pubmed]
  9. Conservation of expression of neuropeptide Y5 receptor between human and rat hypothalamus and limbic regions suggests an integral role in central neuroendocrine control. Nichol, K.A., Morey, A., Couzens, M.H., Shine, J., Herzog, H., Cunningham, A.M. J. Neurosci. (1999) [Pubmed]
  10. NPY regulates catecholamine secretion from human adrenal chromaffin cells. Cavadas, C., Silva, A.P., Mosimann, F., Cotrim, M.D., Ribeiro, C.A., Brunner, H.R., Grouzmann, E. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  11. Overlapping gene structure of the human neuropeptide Y receptor subtypes Y1 and Y5 suggests coordinate transcriptional regulation. Herzog, H., Darby, K., Ball, H., Hort, Y., Beck-Sickinger, A., Shine, J. Genomics (1997) [Pubmed]
  12. Subtype selectivity of the novel nonpeptide neuropeptide Y Y1 receptor antagonist BIBO 3304 and its effect on feeding in rodents. Wieland, H.A., Engel, W., Eberlein, W., Rudolf, K., Doods, H.N. Br. J. Pharmacol. (1998) [Pubmed]
  13. Cloning and characterization of Rhesus monkey neuropeptide Y receptor subtypes. Gehlert, D.R., Yang, P., George, C., Wang, Y., Schober, D., Gackenheimer, S., Johnson, D., Beavers, L.S., Gadski, R.A., Baez, M. Peptides (2001) [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. Evidence for involvement of neuropeptide Y receptors in the regulation of food intake: studies with Y1-selective antagonist BIBP3226. Kask, A., Rägo, L., Harro, J. Br. J. Pharmacol. (1998) [Pubmed]
  16. Discrete distribution of the neuropeptide Y Y5 receptor gene in the human brain: an in situ hybridization study. Jacques, D., Tong, Y., Shen, S.H., Quirion, R. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  17. Novel potent antagonists of human neuropeptide Y Y5 receptors. Part 2: substituted benzo[a]cycloheptene derivatives. Itani, H., Ito, H., Sakata, Y., Hatakeyama, Y., Oohashi, H., Satoh, Y. Bioorg. Med. Chem. Lett. (2002) [Pubmed]
  18. Neuropeptide Y lowers blood glucose in anaesthetized rats via a Y5 receptor subtype. Bischoff, A., Michel, M.C. Endocrinology (1998) [Pubmed]
  19. Pharmacological Characterization and Feeding-Suppressive Property of FMS586 [3-(5,6,7,8-Tetrahydro-9-isopropyl-carbazol-3-yl)-1-methyl-1-(2-pyridin-4-yl-ethyl)-urea Hydrochloride], a Novel, Selective, and Orally Active Antagonist for Neuropeptide Y Y5 Receptor. Kakui, N., Tanaka, J., Tabata, Y., Asai, K., Masuda, N., Miyara, T., Nakatani, Y., Ohsawa, F., Nishikawa, N., Sugai, M., Suzuki, M., Aoki, K., Kitaguchi, H. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  20. From transcription profile to expression: the signaling repertoire of the SK-N-MC neuroepithelioma cell-line. Bader, J.E., Deckert, C.M., Koglin, N., Pluder, F., Mörl, K., Koczan, D., Thiesen, H.J., Beck-Sickinger, A.G. J. Recept. Signal Transduct. Res. (2004) [Pubmed]
  21. Neuropeptide Y induces migration, proliferation, and tube formation of endothelial cells bimodally via Y1, Y2, and Y5 receptors. Movafagh, S., Hobson, J.P., Spiegel, S., Kleinman, H.K., Zukowska, Z. FASEB J. (2006) [Pubmed]
  22. 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]
  23. Characterisation of the neuropeptide Y receptor that mediates feeding in the rat: a role for the Y5 receptor? Haynes, A.C., Arch, J.R., Wilson, S., McClue, S., Buckingham, R.E. Regul. Pept. (1998) [Pubmed]
  24. Comparison of Y-receptor subtype expression in the rat hippocampus. Parker, R.M., Herzog, H. Regul. Pept. (1998) [Pubmed]
  25. Involvement of dopamine D3 and neuropeptide Y Y5 receptors in diabetic gastroparetic rats without response to erythromycin. Qin, X.Y., Wang, Z.G., Fei, J., Liu, F.L., Cui, D.F., Chen, S.L. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (2003) [Pubmed]
  26. Attenuation of circadian light induced phase advances and delays by neuropeptide Y and a neuropeptide Y Y1/Y5 receptor agonist. Lall, G.S., Biello, S.M. Neuroscience (2003) [Pubmed]
  27. Blockade of the NPY Y5 receptor potentiates circadian responses to light: complementary in vivo and in vitro studies. Yannielli, P.C., Brewer, J.M., Harrington, M.E. Eur. J. Neurosci. (2004) [Pubmed]
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