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Gene Review

PYY  -  peptide YY

Homo sapiens

Synonyms: PYY-I, PYY1, Peptide YY, Peptide tyrosine tyrosine
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Disease relevance of PYY

  • In humans and dogs the effects of NPY or PYY were abolished by treatment of cells with Bordetella pertussis toxin, clearly indicating the involvement of a Gi protein in the antilipolytic effects [1].
  • Thus, higher plasma PYY following JIB may contribute to reduced food intake and contribute to weight loss [2].
  • 3-(3-(Benzothiazol-6-yl)ureido)-1-N-(3-(N'-(3-isopropylureido++ +))benzyl )-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (21), which was one of the most potent derivatives, competitively inhibited specific [(125)I]peptide YY (PYY) binding to Y1 receptors in human neuroblastoma SK-N-MC cells (K(i) = 5.1 nM) [3].
  • While obese subjects have appropriate reductions in orexigenic ghrelin, other gut-hormone disturbances may contribute to obesity such as reduced anorexigenic PYY and PP [4].
  • Furthermore, in the patients with colonic inertia, the percentages of strongly and moderately stained PYY-positive cells were higher in the right-side colon than in the left (P < 0.01) [5].

Psychiatry related information on PYY


High impact information on PYY


Chemical compound and disease context of PYY


Biological context of PYY

  • This study indicates that, in addition to alpha 2-adrenergic agonists, NPY and PYY are also involved in the regulation of lipolysis in human and dog adipose tissue as powerful antilipolytic agents [1].
  • Reverse transcriptase-polymerase chain reaction analysis indicated expression also in human cultured vascular smooth muscle cells, supporting the view that the Y1 receptor is associated with NPY/PYY-evoked vasoconstriction [19].
  • We now report the isolation of a human Y2 (hhY2) receptor cDNA by expression cloning from a human hippocampal cDNA library, using a 125I-PYY binding assay. hhY2 cDNA encodes a predicted protein of 381 amino acids with low amino acid identity to the human Y1 receptor (31% overall; 41% transmembrane) [20].
  • Considering the high degree of sequence homology of pNPY and pPYY (>80%) and the fact, that their binding affinities at all receptor subtypes are high and, more importantly, rather similar, it is much more likely that PYY and NPY are recognized by the Y receptors from the membrane-bound state [21].
  • In binding experiments the chimeric peptides were all about equipotent with NPY and PYY in displacing [125I]-PYY from Y1 and Y2 binding sites on SK-N-MC cells and rat hippocampus respectively [22].

Anatomical context of PYY

  • The PYY and RPP antisera labeled groups of neurons and fibers in the rhombencephalic and mesencephalic reticular formation [23].
  • One of the PYY/RPP-ir cell groups, located in the anterior rhombencephalic reticular nucleus, had a projection to the dorsolateral spinal cord [23].
  • NPY is expressed exclusively in neurons, whereas PYY and PP are produced primarily in gut endocrine cells [24].
  • Moreover, the antagonist 1) considerably reversed the PYY-induced reduction of short-circuit current in rat jejunum mucosa in Ussing chamber and 2) completely abolished the antisecretory action of PYY on vasoactive intestinal peptide (VIP)-induced fluid secretion in rat jejunum in vivo [25].
  • BIIE0246 completely abolished the inhibition of cAMP production by PYY in crypt cells and transfected CHO cells [25].

Associations of PYY with chemical compounds

  • Because (a) NPY has been shown to be colocalized with noradrenaline in peripheral as well as central catecholaminergic neurons, and (b) alpha 2-adrenergic receptors of adipocytes play a major role in the regulation of lipolysis, we investigated the effect of NPY and PYY on isolated fat cells [1].
  • 4. Y(1) receptor antagonists, BIBP3226 and BIBO3304 both increased basal I(sc) levels per se and inhibited subsequent PYY and Pro(34)PYY but not hPP or PYY(3 - 36) responses [26].
  • The frequency of PYY-containing cells and the 5-HT-containing cells in the ascending colon was significantly increased in the constipated patients [27].
  • However, as different from the Y1-like LP-PYY binding, but similar to the binding of the Y2-selective ligand [125I]human peptide YY(3-36) (hPYY(3-36)), the PP binding showed a low sensitivity to guanosine polyphosphates [28].
  • PYY inhibits many GI functions, including gastric acid secretion, gastric emptying, small bowel and colonic chloride secretion, mouth to cecum transit time, pancreatic exocrine secretion and pancreatic insulin secretion [29].
  • Our data does not support PYY being relevant in the changes in glucose homeostasis occurring after this type of bariatric surgery [30].

Physical interactions of PYY

  • 1229U91 potently displaced [125I]-peptide YY (PYY) binding to human NPY Y1 receptors (IC50 = 0.245+/-0.004 nM, n = 4). but displayed little affinity for the human NPY Y2 and Y5 receptors (IC50 > 1000 nM) [31].
  • Saturable 125I-porcine PYY binding sites in all regions of the dogfish brain closely resembled the mammalian Y1 NPY receptor subtype in specificity for these substances [32].
  • PYY induced expression of tetraspanins and intestinal fatty acid binding protein (I-FABP) may be part of a mechanism whereby FFA modulate expression of differentiation dependent proteins in the mucosa [33].

Enzymatic interactions of PYY


Co-localisations of PYY

  • GLU was colocalized with PYY and NPY in a few cells in a small peripheral area in the big islet and a few intermediate islets [35].

Regulatory relationships of PYY

  • PYY inhibited the vagal action more effectively than did NPY [36].
  • In the Y1-7 clone, BIBP 3226 fully inhibited the reductions in VIP-stimulated SCC induced by 30 nM PYY, with an IC50 of 27.2 nM and 30 nM BIBP 3226 caused a parallel rightward shift on the PYY concentration-response curve, with an approximate pKB of 8 [37].
  • Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05) [38].
  • PYY inhibits upper gastrointestinal secretory and motor functions [39].
  • This pathway further requires protein kinase C with EGFR TK inhibition blocking PYY-induced protein kinase Cepsilon (PKCepsilon) translocation to the cell membrane [40].

Other interactions of PYY

  • FAT infusion was associated with a marked, and progressive, suppression of plasma ghrelin from t = 60 min (P < 0.001) and stimulation of PYY from t = 30 min (P < 0.01) [41].
  • Peptide YY (PYY) is a 36 amino acid, straight chain polypeptide, which is co-localized with GLP-1 in the L-type endocrine cells of the GI mucosa [29].
  • In obese unoperated patients, the density of PYY and secretin cells was decreased compared with the JIB-patients and the density of the GIP cells compared with both other groups [42].
  • However, other peptides capable of inhibiting gastric acid secretion in vivo, such as CCK, VIP, and PYY, were unable to induce any inhibition of the parietal cell response to db-cAMP or histamine in the isolated gastric gland preparation irrespective of the species studied [43].
  • The levels of VIP, substance P and NPY were higher in the ascending colon than in the descending colon, whereas the opposite pattern was seen for PYY [44].

Analytical, diagnostic and therapeutic context of PYY


  1. Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein. Valet, P., Berlan, M., Beauville, M., Crampes, F., Montastruc, J.L., Lafontan, M. J. Clin. Invest. (1990) [Pubmed]
  2. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. le Roux, C.W., Aylwin, S.J., Batterham, R.L., Borg, C.M., Coyle, F., Prasad, V., Shurey, S., Ghatei, M.A., Patel, A.G., Bloom, S.R. Ann. Surg. (2006) [Pubmed]
  3. 1,3-Disubstituted benzazepines as novel, potent, selective neuropeptide Y Y1 receptor antagonists. Murakami, Y., Hara, H., Okada, T., Hashizume, H., Kii, M., Ishihara, Y., Ishikawa, M., Shimamura, M., Mihara, S., Kato, G., Hanasaki, K., Hagishita, S., Fujimoto, M. J. Med. Chem. (1999) [Pubmed]
  4. Chapter 3: The hypothalamus, hormones, and hunger: alterations in human obesity and illness. Goldstone, A.P. Prog. Brain Res. (2006) [Pubmed]
  5. Abnormality of peptide YY and pancreatic polypeptide immunoreactive cells in colonic mucosa of patients with colonic inertia. Zhao, R.H., Baig, K.M., Wexner, S.D., Woodhouse, S., Singh, J.J., Weiss, E.G., Nogueras, J.J. Dig. Dis. Sci. (2004) [Pubmed]
  6. Neuropeptide Y (NPY)-induced feeding behavior in female rats: comparison with human NPY ([Met17]NPY), NPY analog ([norLeu4]NPY) and peptide YY. Clark, J.T., Sahu, A., Kalra, P.S., Balasubramaniam, A., Kalra, S.P. Regul. Pept. (1987) [Pubmed]
  7. Neuropeptide Y, peptide YY and aluminum in Alzheimer's disease: is there an etiological relationship? Croom, J., Taylor, I.L. J. Inorg. Biochem. (2001) [Pubmed]
  8. Leptin, neuropeptide Y, and peptide YY in long-term recovered eating disorder patients. Gendall, K.A., Kaye, W.H., Altemus, M., McConaha, C.W., La Via, M.C. Biol. Psychiatry (1999) [Pubmed]
  9. Gastric sensorimotor functions and hormone profile in normal weight, overweight, and obese people. Vazquez Roque, M.I., Camilleri, M., Stephens, D.A., Jensen, M.D., Burton, D.D., Baxter, K.L., Zinsmeister, A.R. Gastroenterology (2006) [Pubmed]
  10. Gut and mind. Neary, N.M., Small, C.J., Bloom, S.R. Gut (2003) [Pubmed]
  11. Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36. Pfluger, P.T., Kampe, J., Castaneda, T.R., Vahl, T., D'Alessio, D.A., Kruthaupt, T., Benoit, S.C., Cuntz, U., Rochlitz, H.J., Moehlig, M., Pfeiffer, A.F., Koebnick, C., Weickert, M.O., Otto, B., Spranger, J., Tschöp, M.H. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  12. XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Michel, M.C., Beck-Sickinger, A., Cox, H., Doods, H.N., Herzog, H., Larhammar, D., Quirion, R., Schwartz, T., Westfall, T. Pharmacol. Rev. (1998) [Pubmed]
  13. Peptide YY Levels Are Elevated After Gastric Bypass Surgery. Chan, J.L., Mun, E.C., Stoyneva, V., Mantzoros, C.S., Goldfine, A.B. Obes. Res. (2006) [Pubmed]
  14. Immunohistochemical and ultrastructural studies of twelve argentaffin and six argyrophil carcinoids of the appendix vermiformis. Iwafuchi, M., Watanabe, H., Ajioka, Y., Shimoda, T., Iwashita, A., Ito, S. Hum. Pathol. (1990) [Pubmed]
  15. Central and peripheral regulation of gastric acid secretion by peptide YY. Yang, H. Peptides (2002) [Pubmed]
  16. Adjuvant hormonal treatment with peptide YY or its analog decreases human pancreatic carcinoma growth. Liu, C.D., Rongione, A.J., Garvey, L., Balasubramaniam, A., McFadden, D.W. Am. J. Surg. (1996) [Pubmed]
  17. A potent nonpeptide neuropeptide Y Y1 receptor antagonist, a benzodiazepine derivative. Shigeri, Y., Ishikawa, M., Ishihara, Y., Fujimoto, M. Life Sci. (1998) [Pubmed]
  18. Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind study. Karamanakos, S.N., Vagenas, K., Kalfarentzos, F., Alexandrides, T.K. Ann. Surg. (2008) [Pubmed]
  19. Cloning and functional expression of a human neuropeptide Y/peptide YY receptor of the Y1 type. Larhammar, D., Blomqvist, A.G., Yee, F., Jazin, E., Yoo, H., Wahlested, C. J. Biol. Chem. (1992) [Pubmed]
  20. Expression cloning and pharmacological characterization of a human hippocampal neuropeptide Y/peptide YY Y2 receptor subtype. Gerald, C., Walker, M.W., Vaysse, P.J., He, C., Branchek, T.A., Weinshank, R.L. J. Biol. Chem. (1995) [Pubmed]
  21. Structural similarities of micelle-bound peptide YY (PYY) and neuropeptide Y (NPY) are related to their affinity profiles at the Y receptors. Lerch, M., Mayrhofer, M., Zerbe, O. J. Mol. Biol. (2004) [Pubmed]
  22. Characterization of Y3 receptor-mediated synaptic inhibition by chimeric neuropeptide Y-peptide YY peptides in the rat brainstem. Glaum, S.R., Miller, R.J., Rhim, H., Maclean, D., Georgic, L.M., MacKenzie, R.G., Grundemar, L. Br. J. Pharmacol. (1997) [Pubmed]
  23. Multiple forms of pancreatic polypeptide-related compounds in the lamprey CNS: partial characterization and immunohistochemical localization in the brain stem and spinal cord. Brodin, L., Rawitch, A., Taylor, T., Ohta, Y., Ring, H., Hökfelt, T., Grillner, S., Terenius, L. J. Neurosci. (1989) [Pubmed]
  24. Cloning of a human receptor of the NPY receptor family with high affinity for pancreatic polypeptide and peptide YY. Lundell, I., Blomqvist, A.G., Berglund, M.M., Schober, D.A., Johnson, D., Statnick, M.A., Gadski, R.A., Gehlert, D.R., Larhammar, D. J. Biol. Chem. (1995) [Pubmed]
  25. The peptide YY-preferring receptor mediating inhibition of small intestinal secretion is a peripheral Y(2) receptor: pharmacological evidence and molecular cloning. Goumain, M., Voisin, T., Lorinet, A.M., Ducroc, R., Tsocas, A., Rozé, C., Rouet-Benzineb, P., Herzog, H., Balasubramaniam, A., Laburthe, M. Mol. Pharmacol. (2001) [Pubmed]
  26. Neuropeptide Y, Y1, Y2 and Y4 receptors mediate Y agonist responses in isolated human colon mucosa. Cox, H.M., Tough, I.R. Br. J. Pharmacol. (2002) [Pubmed]
  27. Neuropeptides in idiopathic chronic constipation (slow transit constipation). Sjölund, K., Fasth, S., Ekman, R., Hultén, L., Jiborn, H., Nordgren, S., Sundler, F. Neurogastroenterol. Motil. (1997) [Pubmed]
  28. Characterization of rabbit kidney and brain pancreatic polypeptide-binding neuropeptide Y receptors: differences with Y1 and Y2 sites in sensitivity to amiloride derivatives affecting sodium transport. Parker, S.L., Parker, M.S., Crowley, W.R. Regul. Pept. (1999) [Pubmed]
  29. Peptide YY(1-36) and Peptide YY(3-36): Part I. Distribution, release and actions. Ballantyne, G.H. Obesity surgery : the official journal of the American Society for Bariatric Surgery and of the Obesity Surgery Society of Australia and New Zealand. (2006) [Pubmed]
  30. Circulating peptide YY, weight loss, and glucose homeostasis after gastric bypass surgery in morbidly obese subjects. Morínigo, R., Vidal, J., Lacy, A.M., Delgado, S., Casamitjana, R., Gomis, R. Ann. Surg. (2008) [Pubmed]
  31. The neuropeptide Y Y1 antagonist, 1229U91, a potent agonist for the human pancreatic polypeptide-preferring (NPY Y4) receptor. Schober, D.A., Van Abbema, A.M., Smiley, D.L., Bruns, R.F., Gehlert, D.R. Peptides (1998) [Pubmed]
  32. Localization and characterization of neuropeptide Y/peptide YY receptors in the brain of the smooth dogfish (Mustelis canis). McVey, D.C., Rittschof, D., Mannon, P.J., Vigna, S.R. Regul. Pept. (1996) [Pubmed]
  33. PYY-mediated fatty acid induced intestinal differentiation. Aponte, G.W. Peptides (2002) [Pubmed]
  34. Processing and metabolism of peptide-YY: pivotal roles of dipeptidylpeptidase-IV, aminopeptidase-P, and endopeptidase-24.11. Medeiros, M.D., Turner, A.J. Endocrinology (1994) [Pubmed]
  35. Ontogeny of the endocrine pancreatic cells of the gilthead sea bream, Sparus aurata (Teleost). Navarro, M.H., Lozano, M.T., Agulleiro, B. Gen. Comp. Endocrinol. (2006) [Pubmed]
  36. Neuromodulation of the cardiac vagus: comparison of neuropeptide Y and related peptides. Kilborn, M.J., Potter, E.K., McCloskey, D.I. Regul. Pept. (1985) [Pubmed]
  37. The functional investigation of a human adenocarcinoma cell line, stably transfected with the neuropeptide Y Y1 receptor. Holliday, N.D., Cox, H.M. Br. J. Pharmacol. (1996) [Pubmed]
  38. Effect of rectal distension on gallbladder emptying and circulating gut hormones. van Hoek, F., Mollen, R.M., Hopman, W.P., Kuijpers, H.H., Jansen, J.B. Eur. J. Clin. Invest. (2000) [Pubmed]
  39. Impaired release of peptide YY in patients with proctocolectomy and ileal pouch-anal anastomosis. van Battum, P.L., Hopman, W.P., Salemans, J.M., Kuijpers, J.H., Nagengast, F.M., Jansen, J.B. Scand. J. Gastroenterol. (1999) [Pubmed]
  40. Peptide YY Y1 receptor activates mitogen-activated protein kinase and proliferation in gut epithelial cells via the epidermal growth factor receptor. Mannon, P.J., Mele, J.M. Biochem. J. (2000) [Pubmed]
  41. Fat digestion is required for suppression of ghrelin and stimulation of peptide YY and pancreatic polypeptide secretion by intraduodenal lipid. Feinle-Bisset, C., Patterson, M., Ghatei, M.A., Bloom, S.R., Horowitz, M. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  42. Jejunoileal bypass changes the duodenal cholecystokinin and somatostatin cell density. Ockander, L., Hedenbro, J.L., Rehfeld, J.F., Sjölund, K. Obesity surgery : the official journal of the American Society for Bariatric Surgery and of the Obesity Surgery Society of Australia and New Zealand. (2003) [Pubmed]
  43. Effects of some gastrointestinal peptides on isolated human and rabbit gastric glands. Leth, R., Lundell, L., Olbe, L. Scand. J. Gastroenterol. (1991) [Pubmed]
  44. Abnormal levels of neuropeptide Y and peptide YY in the colon in irritable bowel syndrome. Simrén, M., Stotzer, P.O., Sjövall, H., Abrahamsson, H., Björnsson, E.S. European journal of gastroenterology & hepatology. (2003) [Pubmed]
  45. Expression cloning of a human brain neuropeptide Y Y2 receptor. Gehlert, D.R., Beavers, L.S., Johnson, D., Gackenheimer, S.L., Schober, D.A., Gadski, R.A. Mol. Pharmacol. (1996) [Pubmed]
  46. Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1. Hort, Y., Baker, E., Sutherland, G.R., Shine, J., Herzog, H. Genomics (1995) [Pubmed]
  47. Peptide YY (PYY) and fish pancreatic peptide Y (PY) expression in the brain of the sea bass (Dicentrarchus labrax) as revealed by in situ hybridization. Cerdá-Reverter, J.M., Martínez-Rodríguez, G., Anglade, I., Kah, O., Zanuy, S. J. Comp. Neurol. (2000) [Pubmed]
  48. Significance of gastric endocrine tumor and age-related gut peptide alterations in Mastomys. Bilchik, A.J., Nilsson, O., Modlin, I.M., Zucker, K.A., Adrian, T.E. Regul. Pept. (1990) [Pubmed]
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