Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1987 Apr;84(7):2068–2072. doi: 10.1073/pnas.84.7.2068

Structure and expression of the rat neuropeptide Y gene.

D Larhammar, A Ericsson, H Persson
PMCID: PMC304586  PMID: 3031663

Abstract

Neuropeptide Y is a 36-amino acid peptide that is abundant throughout the mammalian nervous system. It belongs to the same family of carboxyl-terminally amidated peptides as pancreatic polypeptide and peptide YY. We describe here the gene encoding the rat neuropeptide Y precursor. The gene spans 7.2 kilobase pairs and contains four exons. The exon organization is identical to the pancreatic polypeptide gene, although the amino acid sequences of the neuropeptide Y and pancreatic polypeptide precursors differ extensively. The predicted amino acid sequence of mature rat neuropeptide Y is identical to the human sequence. Also the sequence of the 30-amino acid carboxyl-terminal peptide of preproneuropeptide Y is highly conserved, which suggests that it is functionally important. Two neuropeptide Y alleles were found to differ at nine positions in 2.5 kilobase pairs at the 5' portion of the gene. No exon difference was found. One nucleotide substitution close to the gene promoter may influence the regulation of expression. Neuropeptide Y mRNA was found in all rat brain subregions tested, which shows that neuropeptide Y is synthesized throughout the brain. Developmentally, mRNA was detected in the rat brain as early as embryonic day 16 and increased rapidly to adult levels. The level of neuropeptide Y mRNA was also studied in several rat peripheral organs. Unexpectedly high levels were observed in heart and spleen. This mRNA may be synthesized in intrinsic ganglia and non-neuronal cells, respectively.

Full text

PDF
2068

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adrian T. E., Allen J. M., Bloom S. R., Ghatei M. A., Rossor M. N., Roberts G. W., Crow T. J., Tatemoto K., Polak J. M. Neuropeptide Y distribution in human brain. Nature. 1983 Dec 8;306(5943):584–586. doi: 10.1038/306584a0. [DOI] [PubMed] [Google Scholar]
  2. Albers H. E., Ferris C. F. Neuropeptide Y: role in light-dark cycle entrainment of hamster circadian rhythms. Neurosci Lett. 1984 Sep 7;50(1-3):163–168. doi: 10.1016/0304-3940(84)90480-4. [DOI] [PubMed] [Google Scholar]
  3. Allen J. M., Polak J. M., Bloom S. R. Presence of the predicted C-flanking peptide of neuropeptide Y (CPON) in tissue extracts. Neuropeptides. 1985 Apr;6(2):95–100. doi: 10.1016/0143-4179(85)90100-3. [DOI] [PubMed] [Google Scholar]
  4. Allen J. M., Polak J. M., Rodrigo J., Darcy K., Bloom S. R. Localisation of neuropeptide Y in nerves of the rat cardiovascular system and the effect of 6-hydroxydopamine. Cardiovasc Res. 1985 Sep;19(9):570–577. doi: 10.1093/cvr/19.9.570. [DOI] [PubMed] [Google Scholar]
  5. Allen Y. S., Adrian T. E., Allen J. M., Tatemoto K., Crow T. J., Bloom S. R., Polak J. M. Neuropeptide Y distribution in the rat brain. Science. 1983 Aug 26;221(4613):877–879. doi: 10.1126/science.6136091. [DOI] [PubMed] [Google Scholar]
  6. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bell G. I., Selby M. J., Rutter W. J. The highly polymorphic region near the human insulin gene is composed of simple tandemly repeating sequences. Nature. 1982 Jan 7;295(5844):31–35. doi: 10.1038/295031a0. [DOI] [PubMed] [Google Scholar]
  8. Blalock J. E. The immune system as a sensory organ. J Immunol. 1984 Mar;132(3):1067–1070. [PubMed] [Google Scholar]
  9. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  10. Clark J. T., Kalra P. S., Crowley W. R., Kalra S. P. Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Endocrinology. 1984 Jul;115(1):427–429. doi: 10.1210/endo-115-1-427. [DOI] [PubMed] [Google Scholar]
  11. Dalsgaard C. J., Franco-Cereceda A., Saria A., Lundberg J. M., Theodorsson-Norheim E., Hökfelt T. Distribution and origin of substance P- and neuropeptide Y-immunoreactive nerves in the guinea-pig heart. Cell Tissue Res. 1986;243(3):477–485. doi: 10.1007/BF00218054. [DOI] [PubMed] [Google Scholar]
  12. Dynan W. S., Tjian R. Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. 1985 Aug 29-Sep 4Nature. 316(6031):774–778. doi: 10.1038/316774a0. [DOI] [PubMed] [Google Scholar]
  13. Edvinsson L., Ekblad E., Håkanson R., Wahlestedt C. Neuropeptide Y potentiates the effect of various vasoconstrictor agents on rabbit blood vessels. Br J Pharmacol. 1984 Oct;83(2):519–525. doi: 10.1111/j.1476-5381.1984.tb16516.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Everitt B. J., Hökfelt T., Terenius L., Tatemoto K., Mutt V., Goldstein M. Differential co-existence of neuropeptide Y (NPY)-like immunoreactivity with catecholamines in the central nervous system of the rat. Neuroscience. 1984 Feb;11(2):443–462. doi: 10.1016/0306-4522(84)90036-8. [DOI] [PubMed] [Google Scholar]
  15. Gu J., Polak J. M., Allen J. M., Huang W. M., Sheppard M. N., Tatemoto K., Bloom S. R. High concentrations of a novel peptide, neuropeptide Y, in the innervation of mouse and rat heart. J Histochem Cytochem. 1984 May;32(5):467–472. doi: 10.1177/32.5.6546942. [DOI] [PubMed] [Google Scholar]
  16. Hassall C. J., Burnstock G. Neuropeptide Y-like immunoreactivity in cultured intrinsic neurones of the heart. Neurosci Lett. 1984 Nov 23;52(1-2):111–115. doi: 10.1016/0304-3940(84)90359-8. [DOI] [PubMed] [Google Scholar]
  17. Howells R. D., Kilpatrick D. L., Bailey L. C., Noe M., Udenfriend S. Proenkephalin mRNA in rat heart. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1960–1963. doi: 10.1073/pnas.83.6.1960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ivell R., Richter D. The gene for the hypothalamic peptide hormone oxytocin is highly expressed in the bovine corpus luteum: biosynthesis, structure and sequence analysis. EMBO J. 1984 Oct;3(10):2351–2354. doi: 10.1002/j.1460-2075.1984.tb02139.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ivell R., Schmale H., Krisch B., Nahke P., Richter D. Expression of a mutant vasopressin gene: differential polyadenylation and read-through of the mRNA 3' end in a frame-shift mutant. EMBO J. 1986 May;5(5):971–977. doi: 10.1002/j.1460-2075.1986.tb04311.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jarman A. P., Nicholls R. D., Weatherall D. J., Clegg J. B., Higgs D. R. Molecular characterisation of a hypervariable region downstream of the human alpha-globin gene cluster. EMBO J. 1986 Aug;5(8):1857–1863. doi: 10.1002/j.1460-2075.1986.tb04437.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Karlsson S., Nienhuis A. W. Developmental regulation of human globin genes. Annu Rev Biochem. 1985;54:1071–1108. doi: 10.1146/annurev.bi.54.070185.005231. [DOI] [PubMed] [Google Scholar]
  22. Kilpatrick D. L., Howells R. D., Noe M., Bailey L. C., Udenfriend S. Expression of preproenkephalin-like mRNA and its peptide products in mammalian testis and ovary. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7467–7469. doi: 10.1073/pnas.82.21.7467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kozak M. Compilation and analysis of sequences upstream from the translational start site in eukaryotic mRNAs. Nucleic Acids Res. 1984 Jan 25;12(2):857–872. doi: 10.1093/nar/12.2.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Larhammar D., Hammerling U., Rask L., Peterson P. A. Sequence of gene and cDNA encoding murine major histocompatibility complex class II gene A beta 2. J Biol Chem. 1985 Nov 15;260(26):14111–14119. [PubMed] [Google Scholar]
  25. Leiter A. B., Montminy M. R., Jamieson E., Goodman R. H. Exons of the human pancreatic polypeptide gene define functional domains of the precursor. J Biol Chem. 1985 Oct 25;260(24):13013–13017. [PubMed] [Google Scholar]
  26. Lundberg J. M., Saria A., Franco-Cereceda A., Hökfelt T., Terenius L., Goldstein M. Differential effects of reserpine and 6-hydroxydopamine on neuropeptide Y (NPY) and noradrenaline in peripheral neurons. Naunyn Schmiedebergs Arch Pharmacol. 1985 Jan;328(3):331–340. doi: 10.1007/BF00515563. [DOI] [PubMed] [Google Scholar]
  27. Maccarrone C., Jarrott B. Differences in regional brain concentrations of neuropeptide Y in spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. Brain Res. 1985 Oct 14;345(1):165–169. doi: 10.1016/0006-8993(85)90848-0. [DOI] [PubMed] [Google Scholar]
  28. Martel J. C., St-Pierre S., Quirion R. Neuropeptide Y receptors in rat brain: autoradiographic localization. Peptides. 1986 Jan-Feb;7(1):55–60. doi: 10.1016/0196-9781(86)90061-6. [DOI] [PubMed] [Google Scholar]
  29. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  30. Minth C. D., Bloom S. R., Polak J. M., Dixon J. E. Cloning, characterization, and DNA sequence of a human cDNA encoding neuropeptide tyrosine. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4577–4581. doi: 10.1073/pnas.81.14.4577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. O'Donohue T. L., Chronwall B. M., Pruss R. M., Mezey E., Kiss J. Z., Eiden L. E., Massari V. J., Tessel R. E., Pickel V. M., DiMaggio D. A. Neuropeptide Y and peptide YY neuronal and endocrine systems. Peptides. 1985 Jul-Aug;6(4):755–768. doi: 10.1016/0196-9781(85)90180-9. [DOI] [PubMed] [Google Scholar]
  32. Pintar J. E., Schachter B. S., Herman A. B., Durgerian S., Krieger D. T. Characterization and localization of proopiomelanocortin messenger RNA in the adult rat testis. Science. 1984 Aug 10;225(4662):632–634. doi: 10.1126/science.6740329. [DOI] [PubMed] [Google Scholar]
  33. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  34. Rogers J. H. The origin and evolution of retroposons. Int Rev Cytol. 1985;93:187–279. doi: 10.1016/s0074-7696(08)61375-3. [DOI] [PubMed] [Google Scholar]
  35. Sargent T. D., Wu J. R., Sala-Trepat J. M., Wallace R. B., Reyes A. A., Bonner J. The rat serum albumin gene: analysis of cloned sequences. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3256–3260. doi: 10.1073/pnas.76.7.3256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tatemoto K., Carlquist M., Mutt V. Neuropeptide Y--a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature. 1982 Apr 15;296(5858):659–660. doi: 10.1038/296659a0. [DOI] [PubMed] [Google Scholar]
  37. Tatemoto K., Mutt V. Isolation of two novel candidate hormones using a chemical method for finding naturally occurring polypeptides. Nature. 1980 Jun 5;285(5764):417–418. doi: 10.1038/285417a0. [DOI] [PubMed] [Google Scholar]
  38. Undén A., Tatemoto K., Mutt V., Bartfai T. Neuropeptide Y receptor in the rat brain. Eur J Biochem. 1984 Dec 17;145(3):525–530. doi: 10.1111/j.1432-1033.1984.tb08588.x. [DOI] [PubMed] [Google Scholar]
  39. Varndell I. M., Polak J. M., Allen J. M., Terenghi G., Bloom S. R. Neuropeptide tyrosine (NPY) immunoreactivity in norepinephrine-containing cells and nerves of the mammalian adrenal gland. Endocrinology. 1984 Apr;114(4):1460–1462. doi: 10.1210/endo-114-4-1460. [DOI] [PubMed] [Google Scholar]
  40. Whittemore S. R., Ebendal T., Lärkfors L., Olson L., Seiger A., Strömberg I., Persson H. Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system. Proc Natl Acad Sci U S A. 1986 Feb;83(3):817–821. doi: 10.1073/pnas.83.3.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Yaffe D., Nudel U., Mayer Y., Neuman S. Highly conserved sequences in the 3' untranslated region of mRNAs coding for homologous proteins in distantly related species. Nucleic Acids Res. 1985 May 24;13(10):3723–3737. doi: 10.1093/nar/13.10.3723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yamamoto H., Nata K., Okamoto H. Mosaic evolution of prepropancreatic polypeptide. J Biol Chem. 1986 May 15;261(14):6156–6159. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES