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Gene Review

Npy5r  -  neuropeptide Y receptor Y5

Mus musculus

Synonyms: NPY-Y5 receptor, NPY5-R, NPYY5-R, Neuropeptide Y receptor type 5, Npy5, ...
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Disease relevance of Npy5r

  • Chronic neuropeptide Y infusion into the lateral ventricle induces sustained feeding and obesity in mice lacking either Npy1r or Npy5r expression [1].
  • To further investigate the importance of these two receptors in NPY-induced hyperphagia after chronic central administration, we used mice lacking either Npy1r or Npy5r expression [1].
  • The compound did not affect the body weight of lean mice fed a regular diet or genetically obese leptin receptor-deficient mice or rats, despite similarly high brain Y5R receptor occupancy [2].

Psychiatry related information on Npy5r


High impact information on Npy5r

  • We have inactivated the Y5R gene in mice and report that younger Y5R-null mice feed and grow normally; however, they develop mild late-onset obesity characterized by increased body weight, food intake and adiposity [4].
  • Exogenous NPY at physiological concentrations also induces Y5 receptor, stimulates neovascularization, and restores ischemic muscle blood flow and performance [5].
  • The data demonstrate that the NPY Y5 receptor subtype plays a role in NPY-induced food intake, but also suggest that, with chronic blockade, counterregulatory mechanisms are induced to restore appetite [6].
  • The Y5R antagonist selectively ameliorated diet-induced obesity (DIO) in rodents by suppressing body weight gain and adiposity while improving the DIO-associated hyperinsulinemia [2].
  • These data demonstrate that Y5R has an important role in mediating NPY's inhibitory actions in the mouse hippocampus and suggest a role for Y5R in the control of limbic seizures [7].

Biological context of Npy5r


Anatomical context of Npy5r


Associations of Npy5r with chemical compounds

  • CONCLUSIONS: These results indicate that blockade NPY Y5 receptor activity modulates the onset and maintenance of ethanol self-administration [3].
  • METHODS: Effects of the novel NPY Y5 receptor antagonist L-152,804 on the onset and maintenance of operant self-administration were examined in male C57BL/6J mice, which were trained to self-administer ethanol (10% v/v) versus water via the sucrose substitution method during 16 hr overnight sessions [3].
  • We report that Y5R-/- mice do not exhibit spontaneous seizure-like activity; however, they are more sensitive to kainic acid-induced seizures [7].

Other interactions of Npy5r

  • We therefore investigated the central effects of porcine NPY, selective Y1, Y2 and Y5 receptor agonists and a Y1 receptor antagonist on heart rate (HR) and HR variability in freely moving mice using auditory fear conditioning [16].
  • DISCUSSION: Central activation of both Y1 and Y5 receptors increases RQ and adiposity, whereas only Y5 receptor activation reduces energy expended per energy ingested [17].
  • Significant decreases in Y5 receptor mRNA expression were found in the ventromedial, dorsomedial and arcuate hypothalamic nuclei, midline thalamic nuclei, piriform, cingulate and retrosplenial granular cortices of the obese mouse brain [14].
  • Y5 receptor knockout (Y5 -/-) mice on an inbred 129/SvEv background showed normal ethanol-induced locomotor activity and normal voluntary ethanol consumption, but displayed increased sleep time caused by 2.5 and 3.0 g/kg injection of ethanol [18].

Analytical, diagnostic and therapeutic context of Npy5r


  1. Chronic neuropeptide Y infusion into the lateral ventricle induces sustained feeding and obesity in mice lacking either Npy1r or Npy5r expression. Raposinho, P.D., Pedrazzini, T., White, R.B., Palmiter, R.D., Aubert, M.L. Endocrinology (2004) [Pubmed]
  2. A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice. Ishihara, A., Kanatani, A., Mashiko, S., Tanaka, T., Hidaka, M., Gomori, A., Iwaasa, H., Murai, N., Egashira, S., Murai, T., Mitobe, Y., Matsushita, H., Okamoto, O., Sato, N., Jitsuoka, M., Fukuroda, T., Ohe, T., Guan, X., Macneil, D.J., Van der Ploeg, L.H., Nishikibe, M., Ishii, Y., Ihara, M., Fukami, T. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Neuropeptide-Y Y5 receptors modulate the onset and maintenance of operant ethanol self-administration. Schroeder, J.P., Iller, K.A., Hodge, C.W. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
  4. Role of the Y5 neuropeptide Y receptor in feeding and obesity. Marsh, D.J., Hollopeter, G., Kafer, K.E., Palmiter, R.D. Nat. Med. (1998) [Pubmed]
  5. Neuropeptide Y induces ischemic angiogenesis and restores function of ischemic skeletal muscles. Lee, E.W., Michalkiewicz, M., Kitlinska, J., Kalezic, I., Switalska, H., Yoo, P., Sangkharat, A., Ji, H., Li, L., Michalkiewicz, T., Ljubisavljevic, M., Johansson, H., Grant, D.S., Zukowska, Z. J. Clin. Invest. (2003) [Pubmed]
  6. Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor. Criscione, L., Rigollier, P., Batzl-Hartmann, C., Rüeger, H., Stricker-Krongrad, A., Wyss, P., Brunner, L., Whitebread, S., Yamaguchi, Y., Gerald, C., Heurich, R.O., Walker, M.W., Chiesi, M., Schilling, W., Hofbauer, K.G., Levens, N. J. Clin. Invest. (1998) [Pubmed]
  7. Role of the Y5 neuropeptide Y receptor in limbic seizures. Marsh, D.J., Baraban, S.C., Hollopeter, G., Palmiter, R.D. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  8. Evolution of the neuropeptide Y receptor family: gene and chromosome duplications deduced from the cloning and mapping of the five receptor subtype genes in pig. Wraith, A., Törnsten, A., Chardon, P., Harbitz, I., Chowdhary, B.P., Andersson, L., Lundin, L.G., Larhammar, D. Genome Res. (2000) [Pubmed]
  9. Molecular cloning, organization and localization of the gene for the mouse neuropeptide Y-Y5 receptor. Nakamura, M., Yokoyama, M., Watanabe, H., Matsumoto, T. Biochim. Biophys. Acta (1997) [Pubmed]
  10. Y5 receptors mediate neuropeptide Y actions at excitatory synapses in area CA3 of the mouse hippocampus. Guo, H., Castro, P.A., Palmiter, R.D., Baraban, S.C. J. Neurophysiol. (2002) [Pubmed]
  11. Characterization of neuropeptide Y (NPY) Y5 receptor-mediated obesity in mice: chronic intracerebroventricular infusion of D-Trp(34)NPY. Mashiko, S., Ishihara, A., Iwaasa, H., Sano, H., Oda, Z., Ito, J., Yumoto, M., Okawa, M., Suzuki, J., Fukuroda, T., Jitsuoka, M., Morin, N.R., MacNeil, D.J., Van der Ploeg, L.H., Ihara, M., Fukami, T., Kanatani, A. Endocrinology (2003) [Pubmed]
  12. Characterization of neuropeptide Y Y2 and Y5 receptor expression in the mouse hypothalamus. Fetissov, S.O., Byrne, L.C., Hassani, H., Ernfors, P., Hökfelt, T. J. Comp. Neurol. (2004) [Pubmed]
  13. Identification and distribution of mRNA encoding the Y1, Y2, Y4, and Y5 receptors for peptides of the PP-fold family in the rat intestine and colon. Goumain, M., Voisin, T., Lorinet, A.M., Laburthe, M. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  14. Down-regulated NPY receptor subtype-5 mRNA expression in genetically obese mouse brain. Xin, X.G., Huang, X.F. Neuroreport (1998) [Pubmed]
  15. Molecular biology and pharmacology of multiple NPY Y5 receptor species homologs. Borowsky, B., Walker, M.W., Bard, J., Weinshank, R.L., Laz, T.M., Vaysse, P., Branchek, T.A., Gerald, C. Regul. Pept. (1998) [Pubmed]
  16. Central NPY receptor-mediated alteration of heart rate dynamics in mice during expression of fear conditioned to an auditory cue. Tovote, P., Meyer, M., Beck-Sickinger, A.G., von Hörsten, S., Ove Ogren, S., Spiess, J., Stiedl, O. Regul. Pept. (2004) [Pubmed]
  17. Energy metabolic profile of mice after chronic activation of central NPY Y1, Y2, or Y5 receptors. Henry, M., Ghibaudi, L., Gao, J., Hwa, J.J. Obes. Res. (2005) [Pubmed]
  18. Neurobiological responses to ethanol in mutant mice lacking neuropeptide Y or the Y5 receptor. Thiele, T.E., Miura, G.I., Marsh, D.J., Bernstein, I.L., Palmiter, R.D. Pharmacol. Biochem. Behav. (2000) [Pubmed]
  19. Y1-receptors regulate the expression of Y2-receptors in distinct mouse forebrain areas. Wittmann, W., Loacker, S., Kapeller, I., Herzog, H., Schwarzer, C. Neuroscience (2005) [Pubmed]
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