Neuropeptide Y and Related Peptides

C. Wahlestedt
Department of Neurology and Neuroscience
Cornell University Medical College
New York, New York;
current address
Astra Pain Research Unit
Quebec, H7V4A7

Markus Heilig, MD PhD
M46 Addiction Center South
Huddinge University Hospital
S-14186 Huddinge


1. Aicher SA, Springston M, Berger SB, Reis DJ, Wahlestedt C. Receptor-selective analogs demonstrate NPY/PYY receptor heterogeneity in rat brain. Neurosci Lett 1990;130:32–36.

2. Albers HE, Ferris CF, Leeman SE, Goldman BD. Avian pancreatic polypeptide phase shifts hamster circadian rhythms when microinjected into the suprachiasmatic region. Science 1984;223:833–835.

3. Allen JM, Balbi D. Structure and expression of the neuropeptide Y gene. In: Colmers WF, Wahlestedt C, eds. The biology of neuropeptide Y and related peptides. Totowa, NJ: Humana Press, 1993;43–64.

4. Allen J, Novotny J, Martin J, Heinrich G. Molecular structure of mammalian neuropeptide Y: analysis by molecular cloning and computer-aided comparison with crystal structure of avian homologue. Proc Natl Acad Sci USA 1987;84:2532–2536.

5. Andrews PC, Hawke D, Shively JE, Dixon JE. A nonamidated peptide homologous to porcine peptide YY and neuropeptide YY. Endocrinology 1985;116:2677–2681.

6. Aoki C, Pickel VM. Neuropeptide Y in cortex and striatum: ultrastructural distribution and coexistence with classical neurotransmitters and neuropeptides. Ann NY Acad Sci 1990;611:186–205.

7. Bellmann R, Sperk G. Effects of antidepressant drug treatment on levels of NPY or prepro-NPY-mRNA in the rat brain. Neurochem Int 1993;22:183–187.

8. Berrettini WH, Doran AR, Kelsoe J, Roy A, Pickar D. Cerebrospinal fluid neuropeptide Y in depression and schizophrenia. Neuropsychopharmacology 1987;1(1):81–83.

9. Bleakman D, Colmers WF, Fournier A, Miller RJ. Neuropeptide Y inhibits Ca2+ influx into cultured dorsal root ganglion neurones of the rat via a Y2 receptor. Br J Pharmacol 1991;103:1781–1789.

10. Brommé M, Hökfelt T, Terenius L. Peptide YY (PYY)-immunoreactive neurons in the lower brainstem and spinal cord of the rat. Acta Physiol Scand 1985;125:340–352.

11. Chronwall BM, DiMaggio DA, Massari VJ, Pickel VM, Ruggiero DA, O'Donohue TL. The anatomy of neuropeptide-Y-containing neurons in rat brain. Neuroscience 1985;15:1159–1181.

12. Clark JT, Kalra PS, Crowley WR, Kalra SP. Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Endocrinology 1984;115:427–429.

13. Colmers WF, Klapstein GJ, Fournier A, St-Pierre S, Treherne KA. Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor. Br J Pharmacol 1991;102:41–44.

14. De Quidt ME, Emson PC. Distribution of neuropeptide Y-like immunoreactivity in the rat central nervous system. II. Immunohistochemical analysis. Neuroscience 1986;18:545–618.

15. Dumont Y, Fournier A, St Pierre S, Quirion R. Comparative characterization and autoradiographic distribution of neuropeptide Y receptor subtypes in the rat brain. J Neurosci 1993;13:73–86.

16. Ekman R, Wahlestedt C, Böttcher G, Håkanson R, Panula P. Peptide YY-like immunoreactivity in the central nervous system of the rat. Regul Pept 1986;16:157–168.

17. Eva C, Keinänen K, Monyer H, Seeburg P, Sprengel R. Molecular cloning of a novel G protein-coupled receptor that may belong to the neuropeptide receptor family. FEBS Lett 1990;271:80–84.

18. Flood JF, Morley JE. Dissociation of the effects of neuropeptide Y in feeding and memory: evidence for pre- and postsynaptic mediation. Peptides 1989;10:963–966.

19. Fuxe K, Agnati LF, Härfstrand A, Zini I, Tatemoto K, Pich EM, Hökfelt T, Mutt V, Terenius L. Central administration of neuropeptide Y induces hypotension, bradypnea and EEG synchronization in the rat. Acta Physiol Scand 1983;118:189–192.

20. Gray TS, O'Donohue TL, Magnuson DJ. Neuropeptide Y innervation of amygdaloid and hypothalamic neurons that project to the dorsal vagal complex in rat. Peptides 1986;7:341–349.

21. Grundemar L, Sheikh SP, Wahlestedt C. Characterization of receptor types for neuropeptide Y and related peptides. In: Colmers WF, Wahlestedt C, eds. The biology of neuropeptide Y and related peptides. Totowa, NJ: Humana Press, 1993;197–239.

22. Grundemar L, Wahlestedt C, Reis DJ. Neuropeptide Y acts at an atypical receptor to evoke cardiovascular depression and to inhibit glutamate responsiveness in the brainstem. J Pharmacol Exp Ther 1991;258:633–638.

23. Haas DA, George SR. Neuropeptide Y administration acutely increases hypothalamic corticotropin-releasing factor immunoreactivity: lack of effect in other rat brain regions. Life Sci 1987;41:2725–2731.

24. Haas DA, George SR. Neuropeptide Y-induced effects on hypothalamic corticotropin-releasing factor content and release are dependent on noradrenergic/adrenergic neurotransmission. Brain Res 1989;498:333–338.

25. Härfstrand A, Eneroth P, Agnati L, Fuxe K. Further studies on the effects of central administration of neuropeptide Y on neuroendocrine function in the male rat: relationship to hypothalamic catecholamines. Regul Pept 1987;17:167–179.

26. Heilig M, Murison R. Intracerebroventricular neuropeptide Y protects against stress-induced gastric erosion in the rat. Eur J Pharmacol 1987;137:127–129.

27. Heilig M, Murison R. Intracerebroventricular neuropeptide Y suppresses open field and home cage activity in the rat. Regul Pept 1987;19:221–231.

28. Heilig M, Widerlöv E. Neuropeptide Y: an overview of central distribution, functional aspects, and possible involvement in neuropsychiatric illnesses. Acta Psychiatr Scand 1990;82:95–114.

29. Heilig M, McLeod S, Brot M, Heinrichs SC, Menzaghi F, Koob GF, Britton KT. Anxiolytic-like action of neuropeptide Y: mediation by Y1 receptors in amygdala, and dissociation from food intake effects. Neuropsychopharmacology 1993;8(4):357–363.

30. Heilig M, McLeod S, Koob GK, Britton KT. Anxiolytic-like effect of neuropeptide Y (NPY), but not other peptides, in an operant conflict test. Regul Pept 1992;41:61–69.

31. Heilig M, Söderpalm B, Engel JA, Widerlöv E. Centrally administered neuropeptide Y (NPY) produces anxiolytic-like effects in animal anxiety models. Psychopharmacology 1989;98:524–529.

32. Heilig M, Wahlestedt C, Ekman R, Widerlöv E. Antidepressant drugs increase the concentration of neuropeptide Y (NPY)-like immunoreactivity in the rat brain. Eur J Pharmacol 1988;147:465–467.

33. Heilig M, Wahlestedt C, Widerlöv E. Neuropeptide Y (NPY) induced activity suppression in the rat: evidence for NPY receptor heterogeneity and for interaction with a-adrenergic receptors. Eur J Pharmacol 1988;157:205–213.

34. Hendry JHC. Organization of neuropeptide Y neurons in the mammalian central nervous system. In: Colmers WF, Wahlestedt C, eds. The biology of neuropeptide Y and related peptides. Totowa, NJ: Humana Press, 1993;65–156.

35. Herzog H, Hort YJ, Ball HJ, Hayes G, Shine J, Selbie LA. Cloned human neuropeptide Y receptor couples to two different second messenger systems. Proc Natl Acad Sci USA 1992;89:5794–5798.

36. Inoue T, Inui A, Okita M, Sakatani N, Oya M, Morioka H, Mizuno N, Oimomi M, Baba S. Effect of neuropeptide Y on the hypothalamic–pituitary–adrenal axis in the dog. Life Sci 1989; 44:1043–1051.

37. Kalra SP, Dube MG, Sahu A, Phelps CP, Kalra PS. Neuropeptide Y secretion increases in the paraventricular nucleus in association with increased appetite for food. Proc Natl Acad Sci USA 1991;88:10931–10935.

38. Kataoka Y, Sakurai Y, Mine K, Yamashita K, Fujiwara M, Niwa M, Ueki S. The involvement of neuropeptide Y in the antimuricide action of noradrenaline injected into the medial amygdala of olfactory bulbectomized rats. Pharmacol Biochem Behav 1987;28:101–103.

39. Kaye WH, Berrettini WH, Gwirtsman HE, Gold PW, George DT, Jimerson DC, Ebert MH. Contribution of CNS neuropeptide (NPY, CRH, and beta-endorphin) alterations to psychophysiological abnormalities in anorexia nervosa. Psychopharmacol Bull 1989;25:433–438.

40. Kaye WH, Berrettini W, Gwirtsman H, George DT. Altered cerebrospinal fluid neuropeptide Y and peptide YY immunoreactivity in anorexia and bulimia nervosa. Arch Gen Psychiatry 1990;47: 548–556.

41. Kimmel JR, Hayden LJ, Pollock HG. Isolation and characterization of a new pancreatic polypeptide hormone. J Biol Chem 1975; 250:9369–9376.

42. Larhammar D, Blomqvist AG, Yee F, Jazin E, Yoo H, Wahlestedt C. Cloning and functional expression of a human neuropeptide Y/peptide YY receptor of the Y1-type. J Biol Chem 1992;267: 10935–10938.

43. Larhammar D, Söderberg C, Blomqvist AG. Evolution of the neuropeptide Y family of peptides. In: Colmers WF, Wahlestedt C, eds. The biology of neuropeptide Y and related peptides. Totowa, NJ: Humana Press, 1993;1–41.

44. Levine AS, Morley JE. Neuropeptide Y: a potent inducer of consummatory behavior in rats. Peptides 1984;5:1025–1029.

45. Li X-J, Wu Y-N, North A, Forte M. Cloning, functional expression, and developmental regulation of a neuropeptide Y receptor from Drosophila melanogaster. J Biol Chem 1992;267:9–12.

46. Liposits Z, Sievers L, Paull WK. Neuropeptide-Y and ACTHimmunoreactive innervation of corticotropin releasing factor (CRF)-synthesizing neurons in the hypothalamus of the rat. An immunocytochemical analysis at the light and electron microscopic levels. Histochemistry 1988;88:227–234.

47. McQuiston AR, Colmers WF. Neuropeptide Y does not alter NMDA conductances in CA3 pyramidal neurons: a slice-patch study. Neurosci Lett 1992;138:261–264.

48. Minth CD, Bloom SR, Polak JM, Dixon JE. Cloning, characterization, and DNA sequence of a human cDNA encoding neuropeptide tyrosine. Proc Natl Acad Sci USA 1984;81:4577–4581.

49. Monnet FP, Debonnel G, Fournier A, de Montigny C. Neuropeptide Y potentiates N-methyl-D-aspartate response in the CA3 dorsal hippocampus. II. Involvement of a subtype of sigma receptor. J Pharmacol Exp Ther 1992;263:1219–1225.

50. Moore RY, Card JP. Visual pathways and the entrainment of circadian rhythms. Ann NY Acad Sci 1985;453:123–133.

51. Morley JE, Flood JF. The effect of neuropeptide Y on drinking in mice. Brain Res 1989;494:129–137.

52. Roman FJ, Pascaud X, Duffy O, Vauche D, Martin B, Junien JL. Neuropeptide Y and peptide YY interact with rat brain s and PCP binding sites. Eur J Pharmacol 1989;174:301–302.

53. Sabol SL, Higuchi H. Transcriptional regulation of the neuropeptide Y gene by nerve growth factor. Mol Endocrinol 1990;4:384–392.

54. Sahu A, Kalra PS, Kalra SP. Food deprivation and ingestion induce reciprocal changes in neuropeptide Y concentrations in the paraventricular nucleus. Peptides 1988;9:83–86.

55. Shen SH, Grundemar L, Zukowska-Grojec Z, Håkanson R, Wahlestedt C. C-terminal neuropeptide Y fragments are mast celldependent vasodepressor agents. Eur J Pharmacol 1991;204: 249–256.

56. Smialowska M, Legutko B. Influence of imipramine on neuropeptide Y immunoreactivity in the rat brain. Neuroscience 1991;41: 767–771.

57. Stanley BG. Neuropeptide Y in multiple hypothalamic sites controls eating behavior, endocrine, and autonomic systems for body energy balance. In: Colmers WF, Wahlestedt C, eds. The biology of neuropeptide Y and related peptides. Totowa, NJ: Humana Press, 1993;457–509.

58. Stenfors C, Theodorsson E, Mathé AA. Effect of repeated electroconvulsive treatment on regional concentrations of tachykinins, neurotensin, vasoactive intestinal polypeptide, neuropeptide Y, and galanin in rat brain. J Neurosci Res 1989;24:445–450.

59. Suburo AM, Gibson SJ, Moscoso G, Terenghi G, Polak JM. Transient expression of neuropeptide Y and its C-flanking peptide immunoreactivities in the spinal cord and ganglia of human embryos and fetuses. Neuroscience 1992;46:571–584.

60. Sundler F, Böttcher G, Ekblad E, Håkanson R. PP, PYY and NPY—occurrence and distribution in the periphery. In: Colmers WF, Wahlestedt C, eds. The biology of neuropeptide Y and related peptides. Totowa, NJ: Humana Press, 1993;157–196.

61. Tatemoto K. Isolation and characterization of peptide YY (PYY), a candidate gut hormone that inhibits pancreatic exocrine function. Proc Natl Acad Sci USA 1982;79:2514–2518.

62. Tatemoto K, Mutt V. Isolation of two novel candidate hormones using a chemical method for finding naturally occurring polypeptides. Nature 1980;285:417–418.

63. Tatemoto K, Carlquist M, Mutt V. Neuropeptide Y—a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 1982;296:659–660.

64. Tonan K, Kawata Y, Hamaguchi S. Conformations of isolated fragments of pancreatic polypeptide. Biochemistry 1990;29:4424–4429.

65. Tsagarakis S, Rees LH, Besser GM, Grossman A. Neuropeptide-Y stimulates CRF-41 release from rat hypothalami in vitro. Brain Res 1989;502:167–170.

66. Wahlestedt C, Reis DJ. Neuropeptide Y-related peptides and their receptors: are the receptors potential therapeutic drug targets? Annu Rev Pharmacol Toxicol 1993;32:309–352.

67. Wahlestedt C, Blendy JA, Kellar KJ, Heilig M, Widerlov E, Ekman R. Electroconvulsive shocks increase the concentration of neocortical and hippocampal neuropeptide Y (NPY)-like immunoreactivity in the rat. Brain Res 1990;507:65–68.

68. Wahlestedt C, Edvinsson L, Ekblad E, Håkanson R. Effects of neuropeptide Y at sympathetic neuroeffector junctions: existence of Y1- and Y2-receptors. In: Nobin A, Owman C, Arneklo-Nobin B, eds. Neuronal messengers in vascular function. Amsterdam: Elsevier, 1987;231–241.

69. Wahlestedt C, Grundemar L, Håkanson R, Heilig M, Shen GH, Zukowska-Grojec Z, Reis DJ. Neuropeptide Y receptor subtypes, Y1 and Y2. Ann NY Acad Sci 1990;611:7–26.

70. Wahlestedt C, Karoum F, Jaskiw G, Wyatt RJ, Larhammar D, Ekman R, Reis DJ. Cocaine-induced reduction of brain neuropeptide Y synthesis dependent on medial prefrontal cortex. Proc Natl Acad Sci USA 1991;88:2078–2082.

71. Wahlestedt C, Pich EM, Koob GF, Yee F, Heilig M. Modulation of anxiety and neuropeptide Y-Y1 receptors by antisense oligodeoxynucleotides. Science 1993;259:528–531.

72. Wahlestedt C, Skagerberg G, Ekman R, Heilig M, Sundler F, Håkanson R. Neuropeptide Y (NPY) in the area of the hypothalamic paraventricular nucleus activates the pituitary–adrenocortical axis in the rat. Brain Res 1987;417:33–38.

73. Wahlestedt C, Yanaihara N, Håkanson R. Evidence for different pre- and postjunctional receptors for neuropeptide Y and related peptides. Regul Pept 1986;13:307–318.

74. Walker MW, Miller MJ. 125I-neuropeptide Y and 125I-peptide YY bind to multiple receptor sites in rat brain. Mol Pharmacol 1988;34:779–792.

75. Weiner ED, Mallat AM, Papolos DF, Lachman HM. Acute lithium treatment enhances neuropeptide Y gene expression in rat hippocampus. Mol Brain Res 1992;12:209–214.

76. Widdowson PS, Ordway GA, Halaris AE. Reduced neuropeptide Y concentrations in suicide brain. J Neurochem 1992;59:73–80.

77. Widerlöv E, Lindström LH, Wahlestedt C, Ekman R. Neuropeptide Y and peptide YY as possible cerebrospinal markers for major depression and schizophrenia, respectively. J Psychiatr Res 1988;22(1):69–79.

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published 2000