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Gene Review

PPY  -  pancreatic polypeptide

Homo sapiens

Synonyms: PNP, PP, Pancreatic polypeptide, Pancreatic prohormone
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Disease relevance of PPY

  • However, the PPY- and PP-positive cells did not relate to the increased EC. and It is therefore suggested that the altered PYY in the colonic mucosa may partially contribute to the etiopathology of colonic inertia [1].
  • The inhibitory effect of hPP was abolished when cells were incubated with pertussis toxin, indicating a pertussis toxin-sensitive G(i) protein-mediated event [2].
  • The same concentration of antagonist abolished responses to PYY and [Leu31,Pro34]NPY but had no effect upon human pancreatic polypeptide (hPP) in monolayer cultures of the human adenocarcinoma cell line, Colony-6 [3].
  • We propose that estimation of the PP content of medullary carcinoma of thyroid may be a useful means of differentiating familial and sporadic types [4].
  • Implants of diethylstilbestrol inducing anterior pituitary prolactinomas in female Fischer-344 rats produced a considerable elevation of high-affinity binding of either rat or human pancreatic polypeptide (hPP) [5].

Psychiatry related information on PPY


High impact information on PPY


Chemical compound and disease context of PPY


Biological context of PPY


Anatomical context of PPY


Associations of PPY with chemical compounds

  • Second, perturbation of the PP-fold by substitution with a helix-breaking proline residue, resulted in the loss of recognition of the N-terminal segment of the molecule by both types of receptors [27].
  • This recently discovered human intestinal hormonal peptide thus has significant effects both on gastrointestinal hormones (motilin and pancreatic polypeptide) and blood pressure in man, but appears not to influence glucose or lipid metabolism [28].
  • Intracerebroventricular administration of 2 or 10 micrograms of human pancreatic polypeptide to ovariectomized rats pretreated with estradiol benzoate plus progesterone significantly increased the number of animals feeding, and total food intake in tests conducted during the light phase of the day [6].
  • 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 [29].
  • In order to study the physiological significance of the coexistence of pancreatic polypeptide and norepinephrine (NE) in peripheral noradrenergic nerves, the effects of pancreatic polypeptides of several species were tested on the isolated rat vas deferens [30].

Physical interactions of PPY


Regulatory relationships of PPY

  • Activation of extracellular signal regulated protein kinase by neuropeptide Y and pancreatic polypeptide in CHO cells expressing the NPY Y(1), Y(2), Y(4) and Y(5) receptor subtypes [33].
  • 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) [34].
  • Atropine abolished secretory, motor, and pancreatic polypeptide responses to sham feeding and enhanced gastrin release [35].
  • Effects of atropine on GIP-induced insulin and pancreatic polypeptide release in man [36].
  • OBJECTIVE: Intravenously administered secretin stimulates pancreatic polypeptide (PP) release in patients with endocrine enteropancreatic tumors, but data in patients with nontumorous disorders are controversial [37].

Other interactions of PPY

  • Gastrin concentrations were not modified, whereas significant rises were observed in both SS (in a biphasic pattern with peaks at 15 and 120 min) and PP (which increased promptly with a peak at 15 min) [38].
  • PYY caused a significant 50% reduction in plasma pancreatic polypeptide concentrations (P less than 0.05) and a 55% reduction in circulating motilin levels (P less than 0.05) [28].
  • In conclusion, this study clearly demonstrates that ghrelin stimulates SS and PP release in man [38].
  • Pancreatic polypeptide (PP) potently displaced (125)I-1229U91 from the Y4 receptor, but displayed little affinity for Y1 [39].
  • These altered sequences are accompanied by acquisition of new functions apparently unrelated to the neurotransmitter/endocrine role of PYY and PPY, as demonstrated by the major involvement of bovine PYY2, also known as seminal plasmin, in the fertilization process [20].

Analytical, diagnostic and therapeutic context of PPY

  • A second weaker hybridization signal also found on chromosome 17q11 and results obtained by Southern blot analysis suggest that the entire PYY-PPY region has undergone a further duplication event [40].
  • PP-like material was detected in extracts of brain and spinal cord from Lampetra fluviatilis by radioimmunoassay (RIA) using an antiserum to the C-terminal hexapeptide of mammalian PP [24].
  • Members of the PP family regulate numerous physiological processes, including appetite, gastrointestinal transit, anxiety, and blood pressure [41].
  • Immunofluorescence indicated that the Y4 receptor was not internalized within the cells after 24-h treatment with 10 nM hPP [2].
  • This review considers the anorectic peptides PYY, PP, GLP-1, and oxyntomodulin, which decrease appetite and promote satiety in both animal models and humans [42].


  1. 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]
  2. Functional and molecular properties of the human recombinant Y4 receptor: resistance to agonist-promoted desensitization. Voisin, T., Goumain, M., Lorinet, A.M., Maoret, J.J., Laburthe, M. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  3. Selective inhibition of neuropeptide Y Y1 receptors by BIBP3226 in rat and human epithelial preparations. Tough, I.R., Cox, H.M. Eur. J. Pharmacol. (1996) [Pubmed]
  4. Pancreatic polypeptide immunoreactivity in medullary carcinoma of the thyroid: identification and characterisation by radioimmunoassay, immunocytochemistry and high performance liquid chromatography. O'Hare, M.M., Shaw, C., Johnston, C.F., Russell, C.F., Sloan, J.M., Buchanan, K.D. Regul. Pept. (1986) [Pubmed]
  5. Upregulation of pancreatic polypeptide-sensitive neuropeptide Y (NPY) receptors in estrogen-induced hypertrophy of the anterior pituitary gland in the Fischer-344 rat. Parker, M.S., Wang, J.J., Fournier, A., Parker, S.L. Mol. Cell. Endocrinol. (2000) [Pubmed]
  6. Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Clark, J.T., Kalra, P.S., Crowley, W.R., Kalra, S.P. Endocrinology (1984) [Pubmed]
  7. Potential regulators of feeding behavior in anorexia nervosa. Uhe, A.M., Szmukler, G.I., Collier, G.R., Hansky, J., O'Dea, K., Young, G.P. Am. J. Clin. Nutr. (1992) [Pubmed]
  8. Increased plasma pancreatic polypeptide in chronic alcohol abuse. Fink, R.S., Adrian, T.E., Margot, D.H., Bloom, S.R. Clin. Endocrinol. (Oxf) (1983) [Pubmed]
  9. hPP and gastrin response to a liquid meal and oral glucose during prolonged severe exercise, caloric deficit, and sleep deprivation. Oektedalen, O., Flaten, O., Opstad, P.K., Myren, J. Scand. J. Gastroenterol. (1982) [Pubmed]
  10. Interdigestive motor activity in patients with systemic sclerosis. Rees, W.D., Leigh, R.J., Christofides, N.D., Bloom, S.R., Turnberg, L.A. Gastroenterology (1982) [Pubmed]
  11. Brain glucose uptake and unawareness of hypoglycemia in patients with insulin-dependent diabetes mellitus. Boyle, P.J., Kempers, S.F., O'Connor, A.M., Nagy, R.J. N. Engl. J. Med. (1995) [Pubmed]
  12. Preserved insulin secretion and insulin independence in recipients of islet autografts. Pyzdrowski, K.L., Kendall, D.M., Halter, J.B., Nakhleh, R.E., Sutherland, D.E., Robertson, R.P. N. Engl. J. Med. (1992) [Pubmed]
  13. Secretion of pancreatic polypeptide in patients with pancreatic endocrine tumors. Adrian, T.E., Uttenthal, L.O., Williams, S.J., Bloom, S.R. N. Engl. J. Med. (1986) [Pubmed]
  14. Avian pancreatic polypeptide phase shifts hamster circadian rhythms when microinjected into the suprachiasmatic region. Albers, H.E., Ferris, C.F., Leeman, S.E., Goldman, B.D. Science (1984) [Pubmed]
  15. Pancreatic polypeptide is involved in the regulation of body weight in pima Indian male subjects. Koska, J., DelParigi, A., de Courten, B., Weyer, C., Tataranni, P.A. Diabetes (2004) [Pubmed]
  16. Blunted pancreatic polypeptide responses in children with obesity of Prader-Willi syndrome. Zipf, W.B., O'Dorisio, T.M., Cataland, S., Sotos, J. J. Clin. Endocrinol. Metab. (1981) [Pubmed]
  17. Action of omeprazole (a benzimidazole derivative) on secretory responses to sham feeding and pentagastrin and upon serum gastrin and pancreatic polypeptide in duodenal ulcer patients. Konturek, S.J., Kweicień, N., Obtułowicz, W., Kopp, B., Oleksy, J. Gut (1984) [Pubmed]
  18. Basal and postatropine serum pancreatic polypeptide concentrations in familial multiple endocrine neoplasia type I. Lamers, C.B., Diemel, C.M. J. Clin. Endocrinol. Metab. (1982) [Pubmed]
  19. Genes encoding pancreatic polypeptide and neuropeptide Y are on human chromosomes 17 and 7. Takeuchi, T., Gumucio, D.L., Yamada, T., Meisler, M.H., Minth, C.D., Dixon, J.E., Eddy, R.E., Shows, T.B. J. Clin. Invest. (1986) [Pubmed]
  20. Peptide YY-2 (PYY2) and pancreatic polypeptide-2 (PPY2): species-specific evolution of novel members of the neuropeptide Y gene family. Couzens, M., Liu, M., Tüchler, C., Kofler, B., Nessler-Menardi, C., Parker, R.M., Klocker, H., Herzog, H. Genomics (2000) [Pubmed]
  21. The origin and evolution of peptide YY (PYY) and pancreatic polypeptide (PP). Conlon, J.M. Peptides (2002) [Pubmed]
  22. Cloning and functional expression of cDNAs encoding human and rat pancreatic polypeptide receptors. Yan, H., Yang, J., Marasco, J., Yamaguchi, K., Brenner, S., Collins, F., Karbon, W. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  23. The cloned rat pancreatic polypeptide receptor exhibits profound differences to the orthologous receptor. Lundell, I., Statnick, M.A., Johnson, D., Schober, D.A., Starbäck, P., Gehlert, D.R., Larhammar, D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  24. 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]
  25. 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]
  26. Strongly altered receptor binding properties in PP and NPY chimeras are accompanied by changes in structure and membrane binding. Lerch, M., Kamimori, H., Folkers, G., Aguilar, M.I., Beck-Sickinger, A.G., Zerbe, O. Biochemistry (2005) [Pubmed]
  27. The antiparallel pancreatic polypeptide fold in the binding of neuropeptide Y to Y1 and Y2 receptors. Fuhlendorff, J., Johansen, N.L., Melberg, S.G., Thøgersen, H., Schwartz, T.W. J. Biol. Chem. (1990) [Pubmed]
  28. Peptide YY kinetics and effects on blood pressure and circulating pancreatic and gastrointestinal hormones and metabolites in man. Adrian, T.E., Sagor, G.R., Savage, A.P., Bacarese-Hamilton, A.J., Hall, G.M., Bloom, S.R. J. Clin. Endocrinol. Metab. (1986) [Pubmed]
  29. 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]
  30. The effects of pancreatic polypeptides and neuropeptide Y on the rat vas deferens. Ohhashi, T., Jacobowitz, D.M. Peptides (1983) [Pubmed]
  31. Characterization of the peptide binding requirements for the cloned human pancreatic polypeptide-preferring receptor. Gehlert, D.R., Schober, D.A., Beavers, L., Gadski, R., Hoffman, J.A., Smiley, D.L., Chance, R.E., Lundell, I., Larhammar, D. Mol. Pharmacol. (1996) [Pubmed]
  32. Gastrointestinal motor and secretory responses to cholinergic stimulation in humans. Differential modulation by muscarinic and cholecystokinin receptor blockade. Katschinski, M., Steinicke, C., Reinshagen, M., Dahmen, G., Beglinger, C., Arnold, R., Adler, G. Eur. J. Clin. Invest. (1995) [Pubmed]
  33. Activation of extracellular signal regulated protein kinase by neuropeptide Y and pancreatic polypeptide in CHO cells expressing the NPY Y(1), Y(2), Y(4) and Y(5) receptor subtypes. Mullins, D.E., Zhang, X., Hawes, B.E. Regul. Pept. (2002) [Pubmed]
  34. 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]
  35. Cephalic stimulation of gastrointestinal secretory and motor responses in humans. Katschinski, M., Dahmen, G., Reinshagen, M., Beglinger, C., Koop, H., Nustede, R., Adler, G. Gastroenterology (1992) [Pubmed]
  36. Effects of atropine on GIP-induced insulin and pancreatic polypeptide release in man. Amland, P.F., Jorde, R., Burhol, P.G., Giercksky, K.E. Scand. J. Gastroenterol. (1985) [Pubmed]
  37. Plasma pancreatic polypeptide response to secretin. Peracchi, M., Tagliabue, R., Quatrini, M., Reschini, E. Eur. J. Endocrinol. (1999) [Pubmed]
  38. Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels. Arosio, M., Ronchi, C.L., Gebbia, C., Cappiello, V., Beck-Peccoz, P., Peracchi, M. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  39. Pharmacological characterization of (125)I-1229U91 binding to Y1 and Y4 neuropeptide Y/Peptide YY receptors. Schober, D.A., Gackenheimer, S.L., Heiman, M.L., Gehlert, D.R. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  40. 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]
  41. Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY. Bard, J.A., Walker, M.W., Branchek, T.A., Weinshank, R.L. J. Biol. Chem. (1995) [Pubmed]
  42. Gastrointestinal satiety signals III. Glucagon-like peptide 1, oxyntomodulin, peptide YY, and pancreatic polypeptide. Stanley, S., Wynne, K., Bloom, S. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
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