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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
. 1993 Jan 15;90(2):687–691. doi: 10.1073/pnas.90.2.687

Expression of the human neuropeptide tyrosine Y1 receptor.

J Wharton 1, L Gordon 1, J Byrne 1, H Herzog 1, L A Selbie 1, K Moore 1, M H Sullivan 1, M G Elder 1, G Moscoso 1, K M Taylor 1, et al.
PMCID: PMC45729  PMID: 8421707

Abstract

Neuropeptide tyrosine (NPY) is the predominant peptide in the innervation of many human tissues and is considered to play a role in the regulation of blood flow, gastrointestinal secretion and motility, and renal function. Three NPY receptors have been identified (Y1, Y2, and Y3) and the cDNAs encoding the human Y1 and bovine Y3 receptors have recently been cloned. We have demonstrated the expression of the Y1 receptor subtype in several fetal and adult human tissues, including the colon, kidney, adrenal gland, heart, and placenta. A single transcript was identified (approximately 2.2 kb) and localized in tissue sections by in situ hybridization. In the colon the receptor is expressed in the mucosa and basal glands, as well as the myenteric and submucous plexuses. Y1 receptor mRNA was detected in renal collecting ducts, loop of Henle, and juxtaglomerular apparatus and in the syncytiotrophoblast layer of placental villi. Fetal aorta and adult intramyocardial, colonic, and renal blood vessels also exhibited receptor expression, localized to the intima as well as the media. The distribution of Y1 receptor expression correlates with that of NPY-immunoreactive nerves and the apparent actions of NPY in the intestine, kidney, and heart. Although the placenta is devoid of nerves, an NPY-like transcript was detected in the villous trophoblast layer. The results indicate a tissue-specific regulation of NPY Y1 receptor expression.

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Selected References

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  1. Ballesta J., Polak J. M., Allen J. M., Bloom S. R. The nerves of the juxtaglomerular apparatus of man and other mammals contain the potent peptide NPY. Histochemistry. 1984;80(5):483–485. doi: 10.1007/BF00495438. [DOI] [PubMed] [Google Scholar]
  2. Chan-Palay V., Yasargil G., Hamid Q., Polak J. M., Palay S. L. Simultaneous demonstrations of neuropeptide Y gene expression and peptide storage in single neurons of the human brain. Proc Natl Acad Sci U S A. 1988 May;85(9):3213–3215. doi: 10.1073/pnas.85.9.3213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Franco-Cereceda A., Bengtsson L., Lundberg J. M. Inotropic effects of calcitonin gene-related peptide, vasoactive intestinal polypeptide and somatostatin on the human right atrium in vitro. Eur J Pharmacol. 1987 Jan 28;134(1):69–76. doi: 10.1016/0014-2999(87)90132-4. [DOI] [PubMed] [Google Scholar]
  5. Grundemar L., Jonas S. E., Mörner N., Högestätt E. D., Wahlestedt C., Håkanson R. Characterization of vascular neuropeptide Y receptors. Br J Pharmacol. 1992 Jan;105(1):45–50. doi: 10.1111/j.1476-5381.1992.tb14208.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Herzog H., Hort Y. J., Ball H. J., Hayes G., Shine J., Selbie L. A. Cloned human neuropeptide Y receptor couples to two different second messenger systems. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5794–5798. doi: 10.1073/pnas.89.13.5794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jamal H., Jones P. M., Byrne J., Suda K., Ghatei M. A., Kanse S. M., Bloom S. R. Peptide contents of neuropeptide Y, vasoactive intestinal polypeptide, and beta-calcitonin gene-related peptide and their messenger ribonucleic acids after dexamethasone treatment in the isolated rat islets of Langerhans. Endocrinology. 1991 Dec;129(6):3372–3380. doi: 10.1210/endo-129-6-3372. [DOI] [PubMed] [Google Scholar]
  8. Leys K., Schachter M., Sever P. Autoradiographic localisation of NPY receptors in rabbit kidney: comparison with rat, guinea-pig and human. Eur J Pharmacol. 1987 Feb 10;134(2):233–237. doi: 10.1016/0014-2999(87)90171-3. [DOI] [PubMed] [Google Scholar]
  9. Lundberg J. M., Hemsén A., Larsson O., Rudehill A., Saria A., Fredholm B. B. Neuropeptide Y receptor in pig spleen: binding characteristics, reduction of cyclic AMP formation and calcium antagonist inhibition of vasoconstriction. Eur J Pharmacol. 1988 Jan 5;145(1):21–29. doi: 10.1016/0014-2999(88)90344-5. [DOI] [PubMed] [Google Scholar]
  10. Lundberg J. M., Tatemoto K., Terenius L., Hellström P. M., Mutt V., Hökfelt T., Hamberger B. Localization of peptide YY (PYY) in gastrointestinal endocrine cells and effects on intestinal blood flow and motility. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4471–4475. doi: 10.1073/pnas.79.14.4471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Michel M. C. Receptors for neuropeptide Y: multiple subtypes and multiple second messengers. Trends Pharmacol Sci. 1991 Oct;12(10):389–394. doi: 10.1016/0165-6147(91)90610-5. [DOI] [PubMed] [Google Scholar]
  12. Michel M. C., Wirth S. C., Zerkowski H. R., Maisel A. S., Motulsky H. J. Lack of inotropic effects of neuropeptide Y in human myocardium. J Cardiovasc Pharmacol. 1989 Dec;14(6):919–922. doi: 10.1097/00005344-198912000-00019. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Modin A., Pernow J., Lundberg J. M. Evidence for two neuropeptide Y receptors mediating vasoconstriction. Eur J Pharmacol. 1991 Oct 15;203(2):165–171. doi: 10.1016/0014-2999(91)90711-x. [DOI] [PubMed] [Google Scholar]
  15. Persson P. B., Gimpl G., Lang R. E. Importance of neuropeptide Y in the regulation of kidney function. Ann N Y Acad Sci. 1990;611:156–165. doi: 10.1111/j.1749-6632.1990.tb48929.x. [DOI] [PubMed] [Google Scholar]
  16. Petraglia F., Calzà L., Giardino L., Sutton S., Marrama P., Rivier J., Genazzani A. R., Vale W. Identification of immunoreactive neuropeptide-gamma in human placenta: localization, secretion, and binding sites. Endocrinology. 1989 Apr;124(4):2016–2022. doi: 10.1210/endo-124-4-2016. [DOI] [PubMed] [Google Scholar]
  17. Price J. S., Kenny A. J., Huskisson N. S., Brown M. J. Neuropeptide Y (NPY) metabolism by endopeptidase-2 hinders characterization of NPY receptors in rat kidney. Br J Pharmacol. 1991 Oct;104(2):321–326. doi: 10.1111/j.1476-5381.1991.tb12429.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Prieto D., Benedito S., Simonsen U., Nyborg N. C. Regional heterogeneity in the contractile and potentiating effects of neuropeptide Y in rat isolated coronary arteries: modulatory action of the endothelium. Br J Pharmacol. 1991 Mar;102(3):754–758. doi: 10.1111/j.1476-5381.1991.tb12245.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rimland J., Xin W., Sweetnam P., Saijoh K., Nestler E. J., Duman R. S. Sequence and expression of a neuropeptide Y receptor cDNA. Mol Pharmacol. 1991 Dec;40(6):869–875. [PubMed] [Google Scholar]
  20. Sheikh S. P. Neuropeptide Y and peptide YY: major modulators of gastrointestinal blood flow and function. Am J Physiol. 1991 Nov;261(5 Pt 1):G701–G715. doi: 10.1152/ajpgi.1991.261.5.G701. [DOI] [PubMed] [Google Scholar]
  21. Sheikh S. P., Williams J. A. Structural characterization of Y1 and Y2 receptors for neuropeptide Y and peptide YY by affinity cross-linking. J Biol Chem. 1990 May 15;265(14):8304–8310. [PubMed] [Google Scholar]
  22. 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]
  23. Terenghi G., Polak J. M., Hamid Q., O'Brien E., Denny P., Legon S., Dixon J., Minth C. D., Palay S. L., Yasargil G. Localization of neuropeptide Y mRNA in neurons of human cerebral cortex by means of in situ hybridization with a complementary RNA probe. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7315–7318. doi: 10.1073/pnas.84.20.7315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Torda T., Cruciani R. A., Saavedra J. M. Localization of neuropeptide Y binding sites in the zona glomerulosa of the bovine adrenal gland. Neuroendocrinology. 1988 Aug;48(2):207–210. doi: 10.1159/000125010. [DOI] [PubMed] [Google Scholar]
  25. Tseng C. J., Robertson D., Light R. T., Atkinson J. R., Robertson R. M. Neuropeptide Y is a vasoconstrictor of human coronary arteries. Am J Med Sci. 1988 Jul;296(1):11–16. doi: 10.1097/00000441-198807000-00003. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Wharton J., Gulbenkian S., Merighi A., Kuhn D. M., Jahn R., Taylor K. M., Polak J. M. Immunohistochemical and ultrastructural localisation of peptide-containing nerves and myocardial cells in the human atrial appendage. Cell Tissue Res. 1988 Oct;254(1):155–166. doi: 10.1007/BF00220029. [DOI] [PubMed] [Google Scholar]
  28. Wharton J., Polak J. M. Neuropeptide tyrosine in the cardiovascular system. Ann N Y Acad Sci. 1990;611:133–144. doi: 10.1111/j.1749-6632.1990.tb48927.x. [DOI] [PubMed] [Google Scholar]

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