General

Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) are closely related polypeptides based on structural and evolutionary criteria [8,42]. They consist of 36 amino acids (aa) each and share considerable amino acid identity, amidated C-termini and the presence of a large number of tyrosine (abbreviated by the letter Y in the single letter amino acid code) residues including both ends of the molecule (with a few exceptions), hence the name [42]. These peptides also have a characteristic tertiary structure, which has been termed the 'PP-fold' based on crystallography of turkey PP [42]. The PP-fold is U-shaped and consists of an extended polyproline helix and an α-helix connected by a β turn. Endogenously occurring long C-terminal fragments of NPY and PYY, i.e. NPY_3-36 and PYY_3-36 have been described [23,30]. These are not mere degradation products but are actively formed by the enzyme dipeptidyl peptidase IV (also known as CD26) [54], and the occurrence of PYY_3-36 in plasma appears to be regulated by mechanisms that may be distinct from those regulating release of PYY, since physiological stimuli such as food intake may differentially alter the plasma levels of both peptides in man [29].

Endogenous peptides

NPY, PYY and PP can usually be distinguished based on their amino acid sequences [42]. NPY in mammals is primarily synthesised and released by neurones, which in the peripheral nervous system are predominantly sympathetic neurones. PYY is predominantly synthesised and released by intestinal endocrine cells, and can also coexist with glucagon in pancreatic acini and enteroglucagon in endocrine cells of the lower bowel. PP is mainly found in pancreatic cells distinct from those storing insulin, glucagon or somatostatin. However, in some cases other cell types can also express NPY, PYY and PP. While NPY acts as a neurotransmitter, PYY and PP in mammals act as hormones.

Physiological effects attributed to NPY include stimulation of food intake [3,12,44,67], inhibition of anxiety in the CNS [13,35,71], presynaptic inhibition of neurotransmitter release in the CNS and periphery [47], modulation of circadian rhythm [53,74-75], release of pituitary hormones [52,62], modulation of hippocampal activity [14,24,40], pain transmission [9,37], vasoconstriction [48,57], inhibition of insulin release [65,68,70] and modulation of renal function [6,55].

Physiological effects attributed to PYY include slowing of intestinal transit [11,46], inhibition of gastrointestinal anion and electrolyte secretion [15] and appetite inhibition [1,16]. Physiological effects attributed to PP include appetite stimulation [2,41].

While PP was discovered first and NPY last, evolutionary analysis shows that PP actually is the newest member of the family [42]. Both NPY and PYY are found in representatives of all major vertebrate groups. NPY is the most highly conserved; even the sequence in Torpedo marmorata is identical to mammalian NPY in 33 out of 36 positions. PYY and NPY presumably evolved by duplication from a common ancestral gene in an early vertebrate ancestor. These genes are located on different chromosomes. The PP gene arose in a tetrapod ancestor by duplication of the PYY gene; these genes are located close to one another in the same chromosomal segment [42]. Based on these evolutionary considerations, it is recommended that the family is termed the 'NPY family'.

Receptor classification and nomenclature

The members of the NPY family act upon the same family of receptors. Therefore, it is recommended that the receptors for NPY, PYY and PP are classified together as 'NPY receptors' [56]. The NPY receptors are designated by an upper case Y, corresponding to the use in the tyrosine-rich peptide names. The various NPY receptors within the family are designated by subscript numbers, e.g. Y₁, Y₂ etc. While non-mammalian NPY receptor types have been identified that are distinct from all those described below, they are not included in this classification.

At present five distinct NPY receptors have been established by receptor cloning studies. With regard to endogenous agonists, the receptors Y₁, Y₂ and Y₅ preferentially bind NPY and PYY, whereas the Y₄ receptor preferentially binds PP; relative to Y₁ and Y₄ receptors, the Y₂ and Y₅ receptors are also potently activated by NPY_3-36 and PYY_3-36 [27]. The pharmacological profile of the y₆ receptor is controversial; since this 'receptor' is non-functional in primates including humans [31,50] and absent from the rat genome [10], little information has been published following its initial identification.

With regard to synthetic NPY analogues and fragments, the pharmacological profiles of the Y₁ and Y₂ receptors have been clearly established, but those of the Y₄, Y₅ and y₆ receptors require a more extensive investigation, especially with regard to the endogenously expressed receptors. Several NPY responses with a Y₅ receptor-like pharmacological profile have been described in peripheral tissues, but Y₅ receptor mRNA expression is largely restricted to the CNS [7]. The family of NPY receptors can be sorted into three subfamilies [43]: the Y₁ subfamily consisting of subtypes Y₁, Y₄, Y₆ and Y₈ (the latter found in frogs and fishes); the Y₂ subfamily consisting of subtypes Y₂ and Y₇ (the latter found in non-mammalian jawed vertebrates); and the Y₅ subtype remaining alone in a seperate subfamily. All seven of these receptors arose in the vertebrate ancestor whereupon some subtypes were lost in some evolutionary lineages.

Additional sites

It has been reported that PYY is considerably less active than NPY in several model systems including rat CNS [32], rat and bovine adrenals [4,61] and in the adrenal-derived PC12 cell line [51]. This site of action of NPY has been referred to as a 'Y₃ receptor'. However, at present the evidence for the existence of a distinct Y₃ site is circumstantial only, because the receptor has not been cloned and no specific agonists or antagonists have been described. An early report on the cloning of a rat NPY receptor with greater potency for NPY than for PYY [64] was later shown to result from an artefact [36,38]. Therefore, the present evidence is not sufficient to grant the proposed Y₃ site status as a receptor. Since this designation has already been used by various investigators, it is suggested that the third place in the NPY receptor classification is left vacant for the time being and that binding sites and responses where NPY is considerably (at least 10-fold) more potent than PYY are referred to as 'putative Y₃ receptors'.

Several reports have used the term 'PYY-preferring receptor' [33]. In most cases it has been applied to describe a receptor where PYY was three- to five-times more potent than NPY. However, a PYY preference of this small magnitude is observed for many Y₁ receptor-mediated responses and may be a general feature of this receptor rather than the hallmark of an additional type. Thus, convincing evidence for the existence of such a new receptor is lacking.

NPY and related peptides can induce histamine release from mast cells, but it is questionable whether this is a receptor-mediated event [60].

Signal transduction

All NPY receptors couple to pertussis toxin-sensitive G proteins of the G_i or G_o family (inhibition of adenylate cyclase) [56]. Additional signalling responses have been reported but appear to be restricted to certain cell types. These include inhibition of Ca²⁺ channels, e.g. in neurones [25], and activation and inhibition of K⁺ channels, e.g. in cardiomyocytes [58] and vascular smooth muscle cells [73], respectively. Based on experiments with Ca²⁺ entry blockers, it has been postulated that NPY stimulates Ca²⁺ channels in the vasculature [57]. In some cell types members of the NPY family can mobilise Ca²⁺ from intracellular stores; while this appears to involve inositol phosphates in some cells [63], inositol phosphate-independent Ca²⁺ mobilisation has been postulated in other cell types [59]. A sensitivity of certain NPY responses to the cyclooxygenase inhibitor, indomethacin, indicates possible coupling of NPY receptors to a phospholipase A₂ [5,49], but this has yet to be definitively demonstrated. Activation of a phospholipase D or of a tyrosine kinase, which can occur with some G_i/G_o protein-coupled receptors has also not clearly been demonstrated to date, but activation of mitogen-activated protein kinases can occur [39]. Thus, the coupling of NPY receptors to the G_i or G_o protein family, is followed by the responses typically under the control of these G proteins [45]. However, it should be noted that studies with endogenously expressed receptors have mainly been performed with Y₁ receptors (and to a lesser extent with Y₂ receptors), whereas investigations of the signal transduction of other natively expressed NPY receptors are largely missing. Reference [55] outlines the signalling of the NPY receptors.

Pharmacological tools for NPY receptor classification

Historically the subdivision of NPY receptors comes from the observation that C-terminal fragments of NPY or PYY, e.g. NPY_13-36, can mimic some NPY responses, e.g. prejunctional inhibition of twitch responses in the rat vas deferens, but not others, e.g. vasoconstriction in guinea-pig iliac vein [69]. Based on these findings it was proposed that receptors that are only activated by the holopeptides are designated Y₁, while those that are activated by the holopeptides and the C-terminal fragment are designated Y₂. While numerous C-terminal fragments have been synthesised, the 3-36, 13-36 and 18-36 fragments of NPY and PYY are most frequently used without apparent advantages between them. C-terminal NPY fragments are still useful to discriminate Y₁ and Y₂ receptors, but they are not selective for Y₂ receptors since they can also activate Y₅ receptors at similar concentrations [27]. In contrast to NPY and PYY, PP contains a Pro in position 34 of the molecule. [Pro³⁴]-substituted forms of NPY or PYY, i.e. [Leu³¹, Pro³⁴]NPY [61] or [Pro³⁴]PYY are selective for Y₁ relative to Y₂ receptors. An additional [Leu³¹]-substitution in [Pro³⁴]-substituted analogues does not appear to be important for Y₁ selectivity [26,28]. More recent data, however, show that [Pro³⁴]-substituted NPY and PYY analogues also potently activate Y₅ receptors [27].

NPY, PYY, C-terminal fragments and [Pro³⁴]-substituted analogues thereof, and PP are still important tools with which to characterize NPY receptors, particularly since they are commercially available. However, the classification of receptors based on agonists is notoriously unreliable. Moreover, it should be noted, that in some cases the species of origin of the agonist may be important for its potency, and this is particularly true of species variants of PP. Apart from NPY antisera [18], non-selective NPY antagonists have not been described. However, several selective NPY receptor antagonists have now been described. The first small molecule NPY receptor antagonist was BIBP3226, which is selective for Y₁ receptors relative to all other types and for which an inactive stereoisomer is available as a control [21]. A successor of BIBP3226 with similar selectivity but improved potency is BIBO3304 [72]. GR231118 (also known as GW1229 or 1229U91) is another Y₁ receptor-selective antagonist [19,34] but its use is complicated by the fact that it is also a Y₄ agonist [66]. BIIE0246 is a selective Y₂ receptor antagonist [20,22], and CGP71683A is a selective Y₅ receptor antagonist [17]. Several other compounds have been reported to be selective antagonists, but these reports either await confirmation by other laboratories and/or these compounds have not been made freely available to investigators. Overall it should be borne in mind that most of the available tools are not fully selective and that significant differences in receptor affinities for their cognate ligands exist between species. Receptor identification therefore, has to rely on the use of a combination of complementary agents. This caveat applies even more significantly in vivo, where compounds are less characterized than in vitro.

1. Ashby D, Bloom SR. (2007) Recent progress in PYY research--an update report for 8th NPY meeting. Peptides, 28 (2): 198-202. [PMID:17354277]

2. Batterham RL, Le Roux CW, Cohen MA, Park AJ, Ellis SM, Patterson M, Frost GS, Ghatei MA, Bloom SR. (2003) Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab, 88 (8): 3989-92. [PMID:12915697]

3. Beck B. (2006) Neuropeptide Y in normal eating and in genetic and dietary-induced obesity. Philos Trans R Soc Lond, B, Biol Sci, 361 (1471): 1159-85. [PMID:16874931]

4. Bernet F, Maubert E, Bernard J, Montel V, Dupouy JP. (1994) In vitro steroidogenic effects of neuropeptide Y (NPY1-36), Y1 and Y2 receptor agonists (Leu31-Pro34 NPY, NPY18-36) and peptide YY (PYY) on rat adrenal capsule/zona glomerulosa. Regul Pept, 52 (3): 187-93. [PMID:7800851]

5. Bischoff A, Limmroth V, Michel MC. (1998) Indomethacin inhibits the natriuretic effects of neuropeptide Y in anesthetized rats. J Pharmacol Exp Ther, 286 (2): 704-8. [PMID:9694924]

6. Bischoff A, Michel MC. (1998) Renal effects of neuropeptide Y. Pflugers Arch, 435 (4): 443-53. [PMID:9446690]

7. Bischoff A, Michel MC. (1999) Emerging functions for neuropeptide Y5 receptors. Trends Pharmacol Sci, 20 (3): 104-6. [PMID:10203865]

8. Blundell TL, Pitts JE, Tickle IJ, Wood SP, Wu CW. (1981) X-ray analysis (1. 4-A resolution) of avian pancreatic polypeptide: Small globular protein hormone. Proc Natl Acad Sci USA, 78 (7): 4175-9. [PMID:16593056]

9. Brumovsky P, Shi TS, Landry M, Villar MJ, Hökfelt T. (2007) Neuropeptide tyrosine and pain. Trends Pharmacol Sci, 28 (2): 93-102. [PMID:17222466]

10. Burkhoff A, Linemeyer DL, Salon JA. (1998) Distribution of a novel hypothalamic neuropeptide Y receptor gene and it's absence in rat. Brain Res Mol Brain Res, 53 (1-2): 311-6. [PMID:9473707]

11. Cherbut C, Ferrier L, Rozé C, Anini Y, Blottière H, Lecannu G, Galmiche JP. (1998) Short-chain fatty acids modify colonic motility through nerves and polypeptide YY release in the rat. Am J Physiol, 275 (6): G1415-22. [PMID:9843779]

12. Clark JT, Kalra PS, Crowley WR, Kalra SP. (1984) Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Endocrinology, 115 (1): 427-9. [PMID:6547387]

13. Colmers WF, Bleakman D. (1994) Effects of neuropeptide Y on the electrical properties of neurons. Trends Neurosci, 17 (9): 373-9. [PMID:7529442]

14. Colmers WF, Lukowiak K, Pittman QJ. (1987) Presynaptic action of neuropeptide Y in area CA1 of the rat hippocampal slice. J Physiol, 383: 285-299. [PMID:2821236]

15. Cox HM. (2007) Neuropeptide Y receptors; antisecretory control of intestinal epithelial function. Auton Neurosci, 133: 76-85. [PMID:17140858]

16. Cox HM. (2007) Peptide YY: a neuroendocrine neighbor of note. Peptides, 28 (2): 345-51. [PMID:17194503]

17. Criscione L, Rigollier P, Batzl-Hartmann C, Rüeger H, Stricker-Krongrad A, Wyss P, Brunner L, Whitebread S, Yamaguchi Y, Gerald C et al.. (1998) Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor. J Clin Invest, 102 (12): 2136-45. [PMID:9854049]

18. Daly RN, Roberts MI, Ruffolo Jr RR, Hieble JP. (1988) The role of neuropeptide Y in vascular sympathetic neurotransmission may be enhanced in hypertension. J Hypertens Suppl, 6 (4): S535-8. [PMID:2853757]

19. Daniels AJ, Matthews JE, Slepetis RJ, Jansen M, Viveros OH, Tadepalli A, Harrington W, Heyer D, Landavazo A, Leban JJ, Spaltenstein A. (1995) High-affinity neuropeptide Y receptor antagonists. Proc Natl Acad Sci USA, 92: 9067-9071. [PMID:7568074]

20. Doods H, Gaida W, Wieland HA, Dollinger H, Schnorrenberg G, Esser F, Engel W, Eberlein W, Rudolf K. (1999) BIIE0246: a selective and high affinity neuropeptide Y Y(2) receptor antagonist. Eur J Pharmacol, 384 (2-3): R3-5. [PMID:10611450]

21. Doods HN, Wieland HA, Engel W, Eberlein W, Willim KD, Entzeroth M, Wienen W, Rudolf K. (1996) BIBP 3226, the first selective neuropeptide Y1 receptor antagonist: a review of its pharmacological properties. Regul Pept, 65 (1): 71-7. [PMID:8876038]

22. Dumont Y, Cadieux A, Doods H, Pheng LH, Abounader R, Hamel E, Jacques D, Regoli D, Quirion R. (2000) BIIE0246, a potent and highly selective non-peptide neuropeptide Y Y(2) receptor antagonist. Br J Pharmacol, 129 (6): 1075-88. [PMID:10725255]

23. Eberlein GA, Eysselein VE, Schaeffer M, Layer P, Grandt D, Goebell H, Niebel W, Davis M, Lee TD, Shively JE et al.. (1989) A new molecular form of PYY: structural characterization of human PYY(3-36) and PYY(1-36). Peptides, 10 (4): 797-803. [PMID:2587421]

24. El Bahh B, Balosso S, Hamilton T, Herzog H, Beck-Sickinger AG, Sperk G, Gehlert DR, Vezzani A, Colmers WF. (2005) The anti-epileptic actions of neuropeptide Y in the hippocampus are mediated by Y and not Y receptors. Eur J Neurosci, 22 (6): 1417-30. [PMID:16190896]

25. Ewald DA, Sternweis PC, Miller RJ. (1988) Guanine nucleotide-binding protein Go-induced coupling of neuropeptide Y receptors to Ca2+ channels in sensory neurons. Proc Natl Acad Sci USA, 85 (10): 3633-7. [PMID:2453065]

26. Fuhlendorff J, Gether U, Aakerlund L, Langeland-Johansen N, Thøgersen H, Melberg SG, Olsen UB, Thastrup O, Schwartz TW. (1990) [Leu31, Pro34]neuropeptide Y: a specific Y1 receptor agonist. Proc Natl Acad Sci USA, 87 (1): 182-6. [PMID:2153286]

27. Gerald C, Walker MW, Criscione L, Gustafson EL, Batzl-Hartmann C, Smith KE, Vaysse P, Durkin MM, Laz TM, Linemeyer DL et al.. (1996) A receptor subtype involved in neuropeptide-Y-induced food intake. Nature, 382 (6587): 168-71. [PMID:8700207]

28. Grandt D, Feth F, Rascher W, Reeve Jr JR, Schlicker E, Schimiczek M, Layer P, Goebell H, Eysselein VE, Michel MC. (1994) [Pro34]peptide YY is a Y1-selective agonist at peptide YY/neuropeptide Y receptors. Eur J Pharmacol, 269 (2): 127-32. [PMID:7851489]

29. Grandt D, Schimiczek M, Beglinger C, Layer P, Goebell H, Eysselein VE, Reeve Jr JR. (1994) Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1-36 and PYY 3-36. Regul Pept, 51 (2): 151-9. [PMID:8059011]

30. Grandt D, Schimiczek M, Rascher W, Feth F, Shively J, Lee TD, Davis MT, Reeve Jr JR, Michel MC. (1996) Neuropeptide Y 3-36 is an endogenous ligand selective for Y2 receptors. Regul Pept, 67 (1): 33-7. [PMID:8952003]

31. Gregor P, Feng Y, DeCarr LB, Cornfield LJ, McCaleb ML. (1996) Molecular characterization of a second mouse pancreatic polypeptide receptor and its inactivated human homologue. J Biol Chem, 271: 27776-27781. [PMID:8910373]

32. Grundemar L, Wahlestedt C, Reis DJ. (1991) Neuropeptide Y acts at an atypical receptor to evoke cardiovascular depression and to inhibit glutamate responsiveness in the brainstem. J Pharmacol Exp Ther, 258 (2): 633-8. [PMID:1678015]

33. Haynes JM, Hill SJ, Selbie LA. (1997) Neuropeptide Y (NPY) and peptide YY (PYY) effects in the epididymis of the guinea-pig: evidence of a pre-junctional PYY-selective receptor. Br J Pharmacol, 122 (7): 1530-6. [PMID:9421306]

34. Hegde SS, Bonhaus DW, Stanley W, Eglen RM, Moy TM, Loeb M, Shetty SG, DeSouza A, Krstenansky J. (1995) Pharmacological evaluation of 1229U91, a novel high-affinity and selective neuropeptide Y-Y1 receptor antagonist. J Pharmacol Exp Ther, 275 (3): 1261-6. [PMID:8531090]

35. Heilig M. (2004) The NPY system in stress, anxiety and depression. Neuropeptides, 38: 213-224. [PMID:15337373]

36. Herzog H, Hort YJ, Shine J, Selbie LA. (1993) Molecular cloning, characterization, and localization of the human homolog to the reported bovine NPY Y3 receptor: lack of NPY binding and activation. DNA Cell Biol, 12 (6): 465-71. [PMID:8329116]

37. Hua XY, Boublik JH, Spicer MA, Rivier JE, Brown MR, Yaksh TL. (1991) The antinociceptive effects of spinally administered neuropeptide Y in the rat: systematic studies on structure-activity relationship. J Pharmacol Exp Ther, 258 (1): 243-8. [PMID:1677040]

38. Jazin EE, Yoo H, Blomqvist AG, Yee F, Weng G, Walker MW, Salon J, Larhammar D, Wahlestedt C. (1993) A proposed bovine neuropeptide Y (NPY) receptor cDNA clone, or its human homologue, confers neither NPY binding sites nor NPY responsiveness on transfected cells. Regul Pept, 47 (3): 247-58. [PMID:8234909]

39. Keffel S, Schmidt M, Bischoff A, Michel MC. (1999) Neuropeptide-Y stimulation of extracellular signal-regulated kinases in human erythroleukemia cells. J Pharmacol Exp Ther, 291 (3): 1172-8. [PMID:10565839]

40. Klapstein GJ, Colmers WF. (1993) On the sites of presynaptic inhibition by neuropeptide Y in rat hippocampus in vitro. Hippocampus, 3 (1): 103-11. [PMID:8395947]

41. Kojima S, Ueno N, Asakawa A, Sagiyama K, Naruo T, Mizuno S, Inui A. (2007) A role for pancreatic polypeptide in feeding and body weight regulation. Peptides, 28 (2): 459-63. [PMID:17207558]

42. Larhammar D. (1996) Evolution of neuropeptide Y, peptide YY and pancreatic polypeptide. Regul Pept, 62 (1): 1-11. [PMID:8738876]

43. Larhammar D, Salaneck E. (2004) Molecular evolution of NPY receptor subtypes. Neuropeptides, 38 (4): 141-51. [PMID:15337367]

44. Levine AS, Morley JE. (1984) Neuropeptide Y: a potent inducer of consummatory behavior in rats. Peptides, 5 (6): 1025-9. [PMID:6549409]

45. Limbird LE. (1988) Receptors linked to inhibition of adenylate cyclase: additional signaling mechanisms. FASEB J, 2 (11): 2686-95. [PMID:2840317]

46. Lin HC, Neevel C, Chen JH. (2004) Slowing intestinal transit by PYY depends on serotonergic and opioid pathways. Am J Physiol Gastrointest Liver Physiol, 286 (4): G558-63. [PMID:15010361]

47. Lundberg JM. (1996) Pharmacology of cotransmission in the autonomic nervous system: integrative aspects on amines, neuropeptides, adenosine triphosphate, amino acids and nitric oxide. Pharmacol Rev, 48 (1): 113-78. [PMID:8685245]

48. Lundberg JM, Tatemoto K. (1982) Pancreatic polypeptide family (APP, BPP, NPY and PYY) in relation to sympathetic vasoconstriction resistant to alpha-adrenoceptor blockade. Acta Physiol Scand, 116 (4): 393-402. [PMID:6133408]

49. Martin SE, Patterson RE. (1989) Coronary constriction due to neuropeptide Y: alleviation with cyclooxygenase blockers. Am J Physiol, 257 (3 Pt 2): H927-34. [PMID:2506768]

50. Matsumoto M, Nomura T, Momose K, Ikeda Y, Kondou Y, Akiho H, Togami J, Kimura Y, Okada M, Yamaguchi T. (1996) Inactivation of a novel neuropeptide Y/peptide YY receptor gene in primate species. J Biol Chem, 271: 27217-27220. [PMID:8910290]

51. McCullough LA, Westfall TC. (1995) Neuropeptide Y inhibits depolarization-stimulated catecholamine synthesis in rat pheochromocytoma cells. Eur J Pharmacol, 287 (3): 271-7. [PMID:8991801]

52. McDonald JK, Lumpkin MD, Samson WK, McCann SM. (1985) Neuropeptide Y affects secretion of luteinizing hormone and growth hormone in ovariectomized rats. Proc Natl Acad Sci USA, 82 (2): 561-4. [PMID:3855566]

53. Medanic M, Gillette MU. (1993) Suprachiasmatic circadian pacemaker of rat shows two windows of sensitivity to neuropeptide Y in vitro. Brain Res, 620 (2): 281-6. [PMID:8369959]

54. Mentlein R, Dahms P, Grandt D, Krüger R. (1993) Proteolytic processing of neuropeptide Y and peptide YY by dipeptidyl peptidase IV. Regul Pept, 49 (2): 133-44. [PMID:7907802]

55. Michel MC. (2004) Neuropeptide Y and the Kidney. In Neuropeptide Y and Related Peptides (Handbook of Experimental Pharmacology) Vol. 162 Edited by Michel MC (Springer-Verlag) 362-387. [ISBN:354040581X]

56. Michel MC, Beck-Sickinger A, Cox H, Doods HN, Herzog H, Larhammar D, Quirion R, Schwartz T, Westfall T. (1998) XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol Rev, 50 (1): 143-50. [PMID:9549761]

57. Michel MC, Rascher W. (1995) Neuropeptide Y: a possible role in hypertension?. J Hypertens, 13 (4): 385-95. [PMID:7629398]

58. Millar BC, Weis T, Piper HM, Weber M, Borchard U, McDermott BJ, Balasubramaniam A. (1991) Positive and negative contractile effects of neuropeptide Y on ventricular cardiomyocytes. Am J Physiol, 261 (6 Pt 2): H1727-33. [PMID:1661086]

59. Motulsky HJ, Michel MC. (1988) Neuropeptide Y mobilizes Ca2+ and inhibits adenylate cyclase in human erythroleukemia cells. Am J Physiol, 255 (6 Pt 1): E880-5. [PMID:3202164]

60. Mousli M, Landry Y. (1994) Role of positive charges of neuropeptide Y fragments in mast cell activation. Agents Actions, 41 Spec No: C41-2. [PMID:7526655]

61. Nörenberg W, Bek M, Limberger N, Takeda K, Illes P. (1995) Inhibition of nicotinic acetylcholine receptor channels in bovine adrenal chromaffin cells by Y3-type neuropeptide Y receptors via the adenylate cyclase/protein kinase A system. Naunyn Schmiedebergs Arch Pharmacol, 351 (4): 337-47. [PMID:7543184]

62. Pedrazzini T, Pralong F, Grouzmann E. (2003) Neuropeptide Y: the universal soldier. Cell Mol Life Sci, 60 (2): 350-77. [PMID:12678499]

63. Perney TM, Miller RJ. (1989) Two different G-proteins mediate neuropeptide Y and bradykinin-stimulated phospholipid breakdown in cultured rat sensory neurons. J Biol Chem, 264 (13): 7317-27. [PMID:2540185]

64. Rimland J, Xin W, Sweetnam P, Saijoh K, Nestler EJ, Duman RS. (1991) Sequence and expression of a neuropeptide Y receptor cDNA. Mol Pharmacol, 40 (6): 869-75. [PMID:1661837]

65. Sainsbury A, Rohner-Jeanrenaud F, Cusin I, Zakrzewska KE, Halban PA, Gaillard RC, Jeanrenaud B. (1997) Chronic central neuropeptide Y infusion in normal rats: status of the hypothalamo-pituitary-adrenal axis, and vagal mediation of hyperinsulinaemia. Diabetologia, 40 (11): 1269-77. [PMID:9389418]

66. Schober DA, Van Abbema AM, Smiley DL, Bruns RF, Gehlert DR. (1998) The neuropeptide Y Y1 antagonist, 1229U91, a potent agonist for the human pancreatic polypeptide-preferring (NPY Y4) receptor. Peptides, 19 (3): 537-42. [PMID:9533642]

67. Stanley BG, Leibowitz SF. (1984) Neuropeptide Y: stimulation of feeding and drinking by injection into the paraventricular nucleus. Life Sci, 35 (26): 2635-42. [PMID:6549039]

68. Vettor R, Pagano C, Granzotto M, Englaro P, Angeli P, Blum WF, Federspil G, Rohner-Jeanrenaud F, Jeanrenaud B. (1998) Effects of intravenous neuropeptide Y on insulin secretion and insulin sensitivity in skeletal muscle in normal rats. Diabetologia, 41 (11): 1361-7. [PMID:9833945]

69. Wahlestedt C, Yanaihara N, Håkanson R. (1986) Evidence for different pre-and post-junctional receptors for neuropeptide Y and related peptides. Regul Pept, 13 (3-4): 307-18. [PMID:3010387]

70. Wang ZL, Bennet WM, Wang RM, Ghatei MA, Bloom SR. (1994) Evidence of a paracrine role of neuropeptide-Y in the regulation of insulin release from pancreatic islets of normal and dexamethasone-treated rats. Endocrinology, 135 (1): 200-6. [PMID:8013354]

71. Wettstein JG, Earley B, Junien JL. (1995) Central nervous system pharmacology of neuropeptide Y. Pharmacol Ther, 65 (3): 397-414. [PMID:7644568]

72. Wieland HA, Engel W, Eberlein W, Rudolf K, Doods HN. (1998) Subtype selectivity of the novel nonpeptide neuropeptide Y Y1 receptor antagonist BIBO 3304 and its effect on feeding in rodents. Br J Pharmacol, 125: 549-555. [PMID:9806339]

73. Xiong Z, Cheung DW. (1995) ATP-Dependent inhibition of Ca2+-activated K+ channels in vascular smooth muscle cells by neuropeptide Y. Pflugers Arch, 431 (1): 110-6. [PMID:8584407]

74. Yannielli P, Harrington ME. (2004) Let there be "more" light: enhancement of light actions on the circadian system through non-photic pathways. Prog Neurobiol, 74 (1): 59-76. [PMID:15381317]

75. Yannielli PC, Harrington ME. (2001) Neuropeptide Y in the mammalian circadian system: effects on light-induced circadian responses. Peptides, 22 (3): 547-56. [PMID:11287113]