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NPY and energy homeostasis: an opportunity for novel anti-obesity therapies

  • Douglas J. MacNeil
  • Akio Kanatani
Part of the Experientia Supplementum book series (EXS, volume 95)

Keywords

Energy Homeostasis Pancreatic Polypeptide Arcuate Nucleus Orexin Neuron Inhibit Food Intake 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Mokdad A, Ford E, Bowman B, Dietz W, Vinicor F, Bales V, Marks J (2003) Prevalence of obesity, diabetes, and obesity related health risk factors. JAMA 289: 76–79CrossRefPubMedGoogle Scholar
  2. 2.
    Stanley B, Leibowitz S (1985) Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior. PNAS 82: 3940–3943PubMedGoogle Scholar
  3. 3.
    Halaas J, Gajiwala K, Maffei M, Cohen S, Chait B, Rabinowitz D, Lallone R, Burley S, Friedman J (1995) Weight reducing effects of the plasma protein encoded by the obese gene. Science 269: 543–546PubMedGoogle Scholar
  4. 4.
    Stanley B, Magdalin W, Seirafi A, Nguyen M, Leibowitz S (1992) Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y1 receptor mediating this peptide’s effect. Peptides 13: 581–587CrossRefPubMedGoogle Scholar
  5. 5.
    Akabayashi A, Wahlestedt C, Alexander J, Leibowitz S (1994) Specific inhibition of endogenous neuropeptide Y synthesis in arcuate nucleus by antisense oligonucleotides suppresses feeding behavior and insulin secretion. Brain Res Mol Brain Res 21: 55–61PubMedGoogle Scholar
  6. 6.
    Dube M, Xu B, Crowley W, Kalra P, Kalra S (1994) Evidence that neuropeptide Y is a physiological signal for normal food intake. Brain Res 646: 341–344CrossRefPubMedGoogle Scholar
  7. 7.
    Stanley B, Kyrkouli S, Lampert S, Leibowitz SF (1986) Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides 7: 1189–1192PubMedGoogle Scholar
  8. 8.
    Raposinho P, Pedrazzini T, White R, Palmiter R, Aubert M (2004) Chronic neuropeptide Y infusion into the lateral ventricle induces sustained feeding and obesity in mice lacking either Npy1r or Npy5r expression. Endocrinology 145: 304–310PubMedGoogle Scholar
  9. 9.
    Raposinho P, Pierroz D, Broqua P, White R, Pedrazzini T, Aubert M (2001) Chronic administration of neuropeptide Y into the lateral ventricle of C57BL/6J male mice produces an obesity syndrome including hyperphagia, hyperleptinemia, insulin resistance, and hypogonadism. Mol Cell Endocrinol 185: 195–204CrossRefPubMedGoogle Scholar
  10. 10.
    Beck B, Stricker Krongrad A, Nicolas J, Burlet C (1992) Chronic and continuous intracerebroventricular infusion of neuropeptide Y in Long Evans rats mimics the feeding behaviour of obese Zucker rats. Int J Obes Relat Metab Disord 16: 295–302PubMedGoogle Scholar
  11. 11.
    Chamorro S, Della Zuana O, Fauchere J, Feletou M, Galizzi J, Levens N (2002) Appetite suppression based on selective inhibition of NPY receptors. Int J Obes Relat Metab Disord 26: 281–298CrossRefPubMedGoogle Scholar
  12. 12.
    Zimany IA, Fathi Z, Poindexter G (1998) Central control of feeding behavior by neuropeptide Y. Curr Pharm Des 4: 349–366Google Scholar
  13. 13.
    Serradeil Le Gal C, Lafontan M, Raufaste D, Marchand J, Pouzet B, Casellas P, Pascal M, Maffrand J, Le Fur G (2000) Characterization of NPY receptors controlling lipolysis and leptin secretion in human adipocytes. FEBS Lett 475: 150–156PubMedGoogle Scholar
  14. 14.
    Berglund M, Hipskind P, Gehlert DR (2003) Recent developments in our understanding of the physiological role of PP fold peptide receptor subtypes. Exp Biol Med 228: 217–244Google Scholar
  15. 15.
    Sainsbury A, Cooney G, Herzog H (2002) Hypothalamic regulation of energy homeostasis. Best Pract Res Clin Endocrinol Metab 16: 623–637CrossRefPubMedGoogle Scholar
  16. 16.
    Krysiak R, Okopien B, Belowski D, Madej A, Herman Z (2001) Recent insights into body weight control: from physiology to pathology. J Pept Sci 7: 571–578PubMedGoogle Scholar
  17. 17.
    Cone R, Cowley M, Butler A, Fan W, Marks D, Low M (2001) The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int J Obes Relat Metab Disord 25: S63–S67PubMedGoogle Scholar
  18. 18.
    Pinto S, Roseberry A, Liu H, Diano S, Shanabrough M, Cai X, Friedman J, Horvath T (2004) Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 304: 110–115CrossRefPubMedGoogle Scholar
  19. 19.
    Elmquist J (2001) Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin. Physiol Behav 74: 703–708CrossRefPubMedGoogle Scholar
  20. 20.
    de Quidt M, Emson P (1986) Distribution of neuropeptide Y like immunoreactivity in the rat central nervous system II. Immunohistochemical analysis. Neuroscience 18: 545–618PubMedGoogle Scholar
  21. 21.
    Sahu A, Kalra P, Kalra S (1988) Food deprivation and ingestion induced reciprocal changes in neuropeptide Y concentration in the paraventricular nucleus. Peptide 9: 836–886Google Scholar
  22. 22.
    Calza L, Giardino L, Battistini N, Zanni M, Galetti S, Protopapa F, Velardo A (1989) Increase of neuropeptide Y like immunoreactivity in the pareventricular nucleus of fasting rats. Neuroscience Letters 104: 99–104CrossRefPubMedGoogle Scholar
  23. 23.
    Ciofi P, Crowley W, Pillez A, Schmued L, Tramu G, Mazzuca M (1991) Expression of neuropeptide Y precursor immunoreactivity in the hypothalamic dopaminergic tuberoinfundibular system during lactation in rodents. Endocrinology 128: 823–834PubMedGoogle Scholar
  24. 24.
    Smith M (1993) Lactation alters neuropeptide Y and proopiomelanocortin gene expression in the arcuate nucleus of the rat. Endocrinology 133: 1258–1265PubMedGoogle Scholar
  25. 25.
    Kalra S, Dube M, Sahu A, Phelps C, Kalra P (1991) Neuropeptide Y secretion increases in the paraventricular nucleus in association with increased appetite for food. PNAS 88: 10931–10935PubMedGoogle Scholar
  26. 26.
    Stricker Krongrad A, Kozak R, Burlet C, Nicolas J, Beck B (1997) Physiological regulation of hypothalamic neuropeptide Y release in lean and obese rats. Am J Physiol 273: R2112–R2116PubMedGoogle Scholar
  27. 27.
    Schwartz M, Sipols A, Grubin C, Baskin D (1993) Differential effect of fasting on hypothalamic expression of genes encoding neuropeptide Y, galanin, and glutamic acid decarboxylase. Brain Research Bulletin 31: 361–367CrossRefPubMedGoogle Scholar
  28. 28.
    Garcia M, Lopez M, Gualillo O, Seoane L, Dieguez C, Senaris R (2003) Hypothalamic levels of NPY, MCH, and prepro orexin mRNA during pregnancy and lactation in the rat: role of prolactin. FASEB J 17: 1392–1400CrossRefPubMedGoogle Scholar
  29. 29.
    Guan X, Yu H, Trumbauer M, Frazier E, Van der Ploeg L, Chen H (1998) Induction of neuropeptide Y expression in dorsomedial hypothalamus of diet induced obese mice. Neuro Report 9: 3415–3419Google Scholar
  30. 30.
    Guan X, Yu H, Van der Ploeg L (1998) Evidence of altered hypothalamic pro opiomelanocortin/neuropeptide Y mRNA expression in tubby mice. Mol Brain Research 59: 273–279Google Scholar
  31. 31.
    Kesterson R, Huszar D, Lynch C, Simerly R, Cone R (1997) Induction of neuropeptide Y gene expression in the dorsal medial hypothalamic nucleus in two models of the agouti obesity syndrome. Mol Endocrinol 11: 630–637CrossRefPubMedGoogle Scholar
  32. 32.
    Broberger C, Johansen J, Schalling M, Hokfelt T (1997) Hypothalamic neurohistochemistry of the murine anorexia (anx/anx) mutation: altered processing of neuropeptide Y in the arcuate nucleus. J Comp Neuro 387: 124–135Google Scholar
  33. 33.
    Broberger C, Johansen J, Johansson C, Schalling M, Hokfelt T (1998) The neuropeptide Y/agouti gene related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate treated mice. PNAS 95: 15043–15048CrossRefPubMedGoogle Scholar
  34. 34.
    Kanatani A, Ishihara A, Asahi S, Tanaka T, Ozaki S, Ihara M (1996) Potent neuropeptide Y Y1 receptor antagonist, 1229U91: blockade of neuropeptide Y induced and physiological food intake. Endocrinology 137: 3177–3182CrossRefPubMedGoogle Scholar
  35. 35.
    Gerald C, Walker M, Criscione L, Gustafson E, Batzl Hartmann C, Smith K, Vaysse P, Durkin M, Laz T, Linemeyer D et al. (1996) A receptor subtype involved in neuropeptide Y induced food intake. Nature 382: 168–171CrossRefPubMedGoogle Scholar
  36. 36.
    Marsh D, Hollopeter G, Kafer K, Palmiter R (1998) Role of the Y5 neuropeptide Y receptor in feeding and obesity. Nat Med 4: 718–721CrossRefPubMedGoogle Scholar
  37. 37.
    Pedrazzini T, Seydoux J, Kunstner P, Aubert J, Grouzmann E, Beermann F, Brunner H (1998) Cardiovascular response, feeding behavior and locomotor activity in mice lacking the NPY Y1 receptor. Nat Med 46: 722–726Google Scholar
  38. 38.
    Kanatani A, Mashiko S, Murai N, Sugimoto N, Ito J, Fukuroda T, Fukami T, Morin N, MacNeil D, Van der Ploeg L et al. (2000) Role of Y1 receptor in the regulation of neuropeptide Y mediated feeding: comparison of wild type, Y1 receptor deficient, and Y5 receptor deficient mice. Endocrinology 141: 1011–1016CrossRefPubMedGoogle Scholar
  39. 39.
    Sainsbury A, Schwarzer C, Couzens M, Fetissov S, Furtinger S, Jenkins A, Cox H, Sperk G, Hokfelt T, Herzog H (2002) Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice. PNAS 99: 8938–8943CrossRefPubMedGoogle Scholar
  40. 40.
    Batterham R, Cowley M, Small C, Herzog H, Cohen M, Dakin C, Wren A, Brynes A, Low M, Ghatei M et al. (2002) Gut hormone PYY(3–36) physiologically inhibits food intake. Nature 418: 650–654CrossRefPubMedGoogle Scholar
  41. 41.
    Ueno, N Inui, A Iwamoto, M Kaga, T Asakawa, A Okita, M Fujimiya, M Nakajima, Y Ohmoto, Y Ohnaka et al. (1999) Decreased food intake and body weight in pancreatic polypeptide overexpressing mice. Gastroenterology 117: 1427–1432CrossRefPubMedGoogle Scholar
  42. 42.
    Asakawa A, Inui A, Yuzuriha H, Ueno N, Katsuura G, Fujimiya M, Fujino M, Nijima A, Meguid M, Kasuga M (2003) Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology 124: 1325–1336CrossRefPubMedGoogle Scholar
  43. 43.
    Batterham R, Le Roux C, Cohen M, Park A, Ellis S, Patterson M, Frost G, Ghatei M, Bloom S (2003) Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab 88: 3989–3992CrossRefPubMedGoogle Scholar
  44. 44.
    Sainsbury A, Baldock P, Schwarzer C, Ueno N, Enriquez R, Couzens M, Inui A, Herzog H, Gardiner E (2003) Synergistic effects of Y2 and Y4 receptors on adiposity and bone mass revealed in double knockout mice. Mol Cell Biol 23: 5225–5233CrossRefPubMedGoogle Scholar
  45. 45.
    Cheng X, Broberger C, Tong Y, Yongtao X, Ju G, Zhang X, Hokfelt T (1998) Regulation of expression of neuropeptide Y Y1 and Y2 receptors in the arcuate nucleus of fasted rats. Brain Research 792: 89–96CrossRefPubMedGoogle Scholar
  46. 46.
    Zammaretti F, Panzica G, Eva C (2001) Fasting, leptin treatment, and glucose administration differently regulate Y1 receptor gene expression in the hypothalamus of transgenic mice. Endocrinology 142: 3774–3782CrossRefPubMedGoogle Scholar
  47. 47.
    Oberto A, Mele P, Zammaretti F, Panzica G, Eva C (2003) Evidence of altered neuropeptide Y contents and neuropeptide Y1 receptor gene expression in the hypothalamus of pregnant transgenic mice. Endocrinology 144: 4826–4830CrossRefPubMedGoogle Scholar
  48. 48.
    Widdowson P (1997) Regionally selective down regulation of NPY receptor subtypes in the obese Zucker fatty rat, relationship to the Y5 feeding receptor. Brain Research 758: 17–25CrossRefPubMedGoogle Scholar
  49. 49.
    Widdowson P, Upton R, Henderson L, Buckingham R, Wilson S, Williams G (1997) Reciprocal regional changes in brain NPY receptor density during dietary restriction and dietary induced obesity in the rat. Brain Research 774: 1–10CrossRefPubMedGoogle Scholar
  50. 50.
    Xin X, Huang X (1998) Down regulated NPY receptor subtype 5 mRNA expression in genetically obese mouse brain. Neuro Report 9: 737–741Google Scholar
  51. 51.
    Huang X, Han M, Storlien L (2003) The level of NPY receptor mRNA expression in diet induced obese and resistant mice. Mol Brain Research 115: 21–28Google Scholar
  52. 52.
    Small C, Bloom S (2004) Gut hormones as peripheral anti obesity targets. Curr Drug Targets CNS Neurol Disord 3: 379–388CrossRefPubMedGoogle Scholar
  53. 53.
    Asakawa A, Inui A, Ueno N, Fujimiya M, Fujino M, Kasuga M (1999) Mouse pancreatic polypeptide modulates food intake, while not influencing anxiety in mice. Peptides 20: 1445–1448CrossRefPubMedGoogle Scholar
  54. 54.
    Batterham R, Bloom S (2003) The gut hormone peptide YY regulates appetite. Ann N Y Acad Sci 994: 162–168PubMedGoogle Scholar
  55. 55.
    Halatchev I, Ellacott K, Fan W, Cone R (2004) Peptide YY3–36 inhibits food intake in mice through a melanocortin 4 receptor independent mechanism. Endocrinology 145: 2585–2590CrossRefPubMedGoogle Scholar
  56. 56.
    Nonaka N, Shioda S, Niehoff M, Banks W (2003) Characterization of blood brain barrier permeability to PYY3 36 in the mouse. J Pharmacol Exp Ther 306: 948–953CrossRefPubMedGoogle Scholar
  57. 57.
    Kanatani A, Mashiko S, Murai N, Sugimoto N, Ito J, Fukuroda T, Fukami T, Morin N, MacNeil D, Van der Ploeg L et al. (2000) Role of the Y1 receptor in the regulation of neuropeptide Y mediated feeding: comparison of wild type, Y1 receptor deficient, and Y5 receptor deficient mice. Endocrinology 141: 1011–1016CrossRefPubMedGoogle Scholar
  58. 58.
    Batterham R, Cohen M, Ellis S, Le Roux C, Withers D, Frost G, Ghatei M, Bloom S (2003) Inhibition of food intake in obese subjects by peptide YY3–36. N Engl J Med 349: 941–948CrossRefPubMedGoogle Scholar
  59. 59.
    Herzog H (2003) Neuropeptide Y and energy homeostasis: insights from Y receptor knockout models. Eur J Pharmacol 480: 21–29CrossRefPubMedGoogle Scholar
  60. 60.
    Erickson J, Clegg K, Palmiter R (1996) Sensitivity to leptin and susceptibility to seizures of mice lacking neuropeptide Y. Nature 381: 415–421CrossRefPubMedGoogle Scholar
  61. 61.
    Segal Lieberman G, Trombly D, Juthani V, Wang X, Maratos Flier E (2003) NPY ablation in C57BL/6 mice leads to mild obesity and to an impaired refeeding response to fasting. Am J Physiol Endocrinol Metab 284: E1131–1139PubMedGoogle Scholar
  62. 62.
    Qian S, Chen H, Weingarth D, Trumbauer M, Novi D, Guan X, Yu H, Shen Z, Feng Y, Frazier E et al. (2002) Neither agouti related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice. Mol Cell Biol 22: 5027–5035CrossRefPubMedGoogle Scholar
  63. 63.
    Hohmann J, Teklemichael D, Weinshenker D, Wynick D, Clifton D, Steiner RA (2004) Obesity and endocrine dysfunction in mice with deletions of both neuropeptide Y and galanin. Mol Cell Biol 24: 2978–2985CrossRefPubMedGoogle Scholar
  64. 64.
    Erickson J, Hollopeter G, Palmiter R (1996) Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. Science 274: 1704–1707CrossRefPubMedGoogle Scholar
  65. 65.
    Kushi A, Sasai H, Koizumi H, Takeda N, Yokoyama M, Nakamura M (1998) Obesity and mild hyperinsulinemia found in neuropeptide Y Y1 receptor deficient mice. PNAS 95: 15659–15664CrossRefPubMedGoogle Scholar
  66. 66.
    Pralong F, Gonzales C, Voirol M, Palmiter R, Brunner H, Gaillard R, Seydoux J, Pedrazzini T (2002) The neuropeptide Y Y1 receptor regulates leptin mediated control of energy homeostasis and reproductive functions. FASEB J 16: 712–714PubMedGoogle Scholar
  67. 67.
    King P, Williams G, Doods H, Widdowson P (2000) Effect of a selective neuropeptide Y Y(2) receptor antagonist, BIIE0246 on neuropeptide Y release. Eur J Pharmacol 396: R1–R3CrossRefPubMedGoogle Scholar
  68. 68.
    Naveilhan P, Hassani H, Canals J, Ekstrand A, Larefalk A, Chhajlani V, Arenas E, Gedda K, Svensson L, Thoren P et al. (1999) Normal feeding behavior, body weight and leptin response require the neuropeptide Y Y2 receptor. Nat Med 5: 1188–1193CrossRefPubMedGoogle Scholar
  69. 69.
    Sainsbury A, Schwarzer C, Couzens M, Herzog H (2002) Y2 receptor deletion attenuates the type 2 diabetic syndrome of ob/ob mice. Diabetes 51: 3420–3427PubMedGoogle Scholar
  70. 70.
    Sainsbury A, Schwarzer C, Couzens M, Jenkins A, Oakes S, Ormandy C, Herzog H (2002) Y4 receptor knockout rescues fertility in ob/ob mice. Genes Dev 16: 1077–1088CrossRefPubMedGoogle Scholar
  71. 71.
    Clark JT, Clark J, Kalra P, Crowley W, Kalra S (1984) Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Endocrinology 115: 427–429PubMedGoogle Scholar
  72. 72.
    Parrott R, Heavens R, Baldwin B (1986) Stimulation of feeding in the satiated pig by intracerebroventricular injection of neuropeptide Y. Physiol Behv 36: 523–525Google Scholar
  73. 73.
    Sakatani N, Inui A, Inoue T, Oya M, Morioka H, Baba S (1987) The role of cholecystokinin octapeptide in the central control of food intake in dog. Peptides 8: 651–656CrossRefPubMedGoogle Scholar
  74. 74.
    Miner J, Della-Fera M, Paterson J, Baile C (1989) Lateral cerebroventricular injection of neuropeptide Y stimulates feeding in sheep. Am J Physiol 257: R383–R387PubMedGoogle Scholar
  75. 75.
    Larsen P, Tang-Christensen M, Stidsen C, Madsen K, Smith M, Cameron J (1999) Activation of central neuropeptide Y Y1 receptors potently stimulates food intake in male rhesus monkeys. J Clin Endocrinol Metab 84: 3781–3791CrossRefPubMedGoogle Scholar
  76. 76.
    Zarjevski N, Cusin I, Vettor R, Rohner-Jeanrenaud F, Jeanrenaud B (1993) Chronic intracerebroventricular neuropeptide Y administration to normal rats mimics hormonal and metabolic changes of obesity. Endocrinology 133: 1753–1758CrossRefPubMedGoogle Scholar
  77. 77.
    Raposinho P, Pierroz D, Broqua P, White R, Pedrazzini T, Aubert M (2001) Chronic administration of neuropeptide Y into the lateral ventricle of C57BL/6J male mice produces an obesity syndrome including hyperpagia, hyperinsulinemia, insulin resistance and hypogonandism. Mol Cell Endocrinol 185: 195–204CrossRefPubMedGoogle Scholar
  78. 78.
    Soll R, Dinger M, Lundell I, Larhammer D, Beck-Sickinger A (2001) Novel analogues of neuropeptide Y with a preference for the Y1 receptor. Eur J Biochem 268: 2828–2837CrossRefPubMedGoogle Scholar
  79. 79.
    Mullins D, Kirby D, Hwa J, Guzzi M, Rivier J, Parker E (2001) Identification of potent and selective neuropeptide Y Y1 receptor agonists with orexigenic activity in vivo. Mol Pharmacol 60: 534–540PubMedGoogle Scholar
  80. 80.
    Parker E, Balasubramaniam A, Guzzi M, Mullins D, Salisbury B, Sheriff S, Witten M, Hwa J (2000) [D Trp34]neuropeptide Y is a potent and selective neuropeptide Y Y5 receptor agonist with dramatic effects on food intake. Peptides 21: 393–399CrossRefPubMedGoogle Scholar
  81. 81.
    Cabrele C, Langer M, Bader R, Wieland H, Doods H, Zerbe O, Beck-Sickinger A (2000) The first selective agonist for the neuropeptide YY5 receptor increases food intake in rats. J Biol Chem 275: 36043–36048CrossRefPubMedGoogle Scholar
  82. 82.
    Cabrele C, Wieland H, Koglin N, Stidsen C, Beck-Sickinger A (2002) Ala31 Aib32: identification of the key motif for high affinity and selectivity of neuropeptide Y at the Y5 receptor. Biochemistry 41: 8043–8049CrossRefPubMedGoogle Scholar
  83. 83.
    Balasubramaniam A, Sheriff S, Zhai W, Chance W (2002) Bis(31/31′)[Cys31,Nva34]NPY(27–36) NH2: a neuropeptide Y (NPY) Y5 receptor selective agonist with a latent stimulatory effect on food intake in rats. A. Peptides 23: 1485–1490CrossRefPubMedGoogle Scholar
  84. 84.
    Mashiko S, Ishihara A, Iwaasa H, Sano H, Oda Z, Ito J, Yumoto M, Okawa M, Suzuki J, Fukuroda T et al. (2003) Characterization of neuropeptide Y (NPY) Y5 receptor mediated obesity in mice: chronic intrecerebroventricular infusion of D Trp34NPY. S. Endocrinology 144: 1793–1801CrossRefPubMedGoogle Scholar
  85. 85.
    Wyss P, Stricker-Krongrad A, Brunner L, Miller J, Crossthwaite A, Whitebread S, Criscione L (1998) The pharmacology of neuropeptide Y (NPY) receptor mediated feeding in rats characterizes better Y5 than Y1, but not Y2 or Y4 subtypes. Regul Pept 75/76: 363–371CrossRefGoogle Scholar
  86. 86.
    Haynes A, Arch J, Wilson S, McClue S, Buckingham R (1998) Characterization of the neuropeptide Y receptor that mediates feeding in the rat: a role for the Y5 receptor. Regul Pept 75/76: 355–361CrossRefGoogle Scholar
  87. 87.
    Campbell R, Smith M, Allen S, Grayson B, Ffrench-Mullen J, Grove K (2003) Orexin neuron express a functional pancreatic polypeptide Y4 receptor. J Neuroscience 23: 1487–1497Google Scholar
  88. 88.
    Broberger C, Landry M, Wong H, Walsh J, Hokfelt T (1997) Subtypes Y1 and Y2 of the neuropeptide Y receptor are respectively expressed in pro opiomelanocortin and neuropeptide Y containing neurons of the rat hypothalamic arcuate nucleus. Neuroendocrinol 66: 393–408Google Scholar
  89. 89.
    Lin S, Boey D, Couzens M, Lee N, Sainsbury A, Herzog H (2005) Compensatory changes in [125I] PYY binding in Y receptor knockout mice suggest the potential existence of further Y receptor(s). Neuropeptides 39: 21–28CrossRefPubMedGoogle Scholar
  90. 90.
    Challis B, Pinnock S, Coll A, Carter R, Dickson S, O’Rahilly S (2003) Acute effects of PYY3–36 on food intake and hypothalamic neuropeptide expression in the mouse. Biochem Biophys Res Comm 311: 915–919CrossRefPubMedGoogle Scholar
  91. 91.
    Koda S et al. (2005) The role of the vagal nerve in peripheral PYY3-36 induced feeding reduction in rats. Endocrinology 146: 2369–2375CrossRefPubMedGoogle Scholar
  92. 92.
    Sato N, Takahashi T, Shibata T, Haga Y, Sakuraba A, Hirose M, Sato M, Nonoshita K, Koike Y, Kitazawa H et al. (2003) Design and synthesis of the potent, orally available, brain penetrable arylpyrazole class of neuropeptide Y5 receptor antagonists. J Med Chem 246: 666–669Google Scholar
  93. 93.
    Kanatani A, Ishihara A, Iwaasa H, Nakamura K, Okamoto O, Hidaka M, Ito J, Fukuroda T, MacNeil D, Van der Ploeg L et al. (2000) L-152,804: orally active and selective neuropeptide Y Y5 receptor antagonist. Biochem Biophys Res Commun 272: 169–173CrossRefPubMedGoogle Scholar
  94. 94.
    Kanatani A, Kanno T, Ishihara A, Hata M, Sakuraba A, Tanaka T, Tsuchiya Y, Mase T, Fukuroda T, Fukami T et al. (1999) The novel neuropeptide Y Y(1) receptor antagonist J 104870: a potent feeding suppressant with oral bioavailability. Biochem Biophys Res Commun 266: 88–91CrossRefPubMedGoogle Scholar
  95. 95.
    Kanatani A, Hata M, Mashiko S, Ishihara A, Okamoto O, Haga Y, Ohe T, Kanno T, Murai N, Ishii Y et al. (2001) A typical Y1 receptor regulates feeding behaviors: effects of a potent and selective Y1 antagonist, J-115814. Mol Pharmacol 3: 501–505Google Scholar
  96. 96.
    Ishihara A, Kanatani A, Okada M, Hidaka M, Tanaka T, Mashiko S, Gomori A, Kanno T, Hata M, Kanesaka M et al. (2002) Blockade of body weight gain and plasma corticosterone levels in Zucker fatty rats using an orally active neuropeptide Y Y1 antagonist. Br J Pharmacol 1363: 341–346Google Scholar
  97. 97.
    Turnbull A, Ellershaw L, Masters D, Birtles S, Boyer S, Carroll D, Clarkson P, Loxham S, McAulay P, Teague J et al. (2002) Selective antagonism of the NPY Y5 receptor does not have a major effect on feeding in rats. Diabetes 51: 2441–2449PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2006

Authors and Affiliations

  • Douglas J. MacNeil
    • 1
  • Akio Kanatani
    • 2
  1. 1.Metabolic DisordersMerck Research LaboratoriesRahwayUSA
  2. 2.Metabolic DisordersBanyu Tsukuba Research InstituteTsukubaJapan

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