Abstract
Neuropeptide Y (NPY) is one of the most abundant neuropeptides in the mammalian nervous system and exhibits a diverse range of important physiological activities, including effects on psychomotor activity, food intake, regulation of central endocrine secretion, and potent vasoactive effects on the cardiovascular system. Two major subtypes of NPY receptor (Y1 and Y2) have been defined by pharmacological criteria. We report here the molecular cloning of a cDNA sequence encoding a human NPY receptor and the corrected sequence for a rat homologue. Analysis of this sequence confirms that the receptor is a member of the G protein-coupled receptor superfamily. When expressed in Chinese hamster ovary (CHO) or human embryonic kidney (293) cells, the receptor exhibits the characteristic ligand specificity of a Y1 type of NPY receptor. In the 293 cell line, the receptor is coupled to a pertussis toxin-sensitive G protein that mediates the inhibition of cyclic AMP accumulation. In the CHO cell line, the receptor is coupled not to the inhibition of adenylate cyclase but rather to the elevation of intracellular calcium. These results demonstrate that second messenger coupling of the NPY-Y1 receptor is cell type specific, depending on the specific repertoire of G proteins and effector systems present in any cell type.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aakerlund L., Gether U., Fuhlendorff J., Schwartz T. W., Thastrup O. Y1 receptors for neuropeptide Y are coupled to mobilization of intracellular calcium and inhibition of adenylate cyclase. FEBS Lett. 1990 Jan 15;260(1):73–78. doi: 10.1016/0014-5793(90)80069-u. [DOI] [PubMed] [Google Scholar]
- 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]
- Eva C., Keinänen K., Monyer H., Seeburg P., Sprengel R. Molecular cloning of a novel G protein-coupled receptor that may belong to the neuropeptide receptor family. FEBS Lett. 1990 Oct 1;271(1-2):81–84. doi: 10.1016/0014-5793(90)80377-u. [DOI] [PubMed] [Google Scholar]
- Fuhlendorff J., Gether U., Aakerlund L., Langeland-Johansen N., Thøgersen H., Melberg S. G., Olsen U. B., Thastrup O., Schwartz T. W. [Leu31, Pro34]neuropeptide Y: a specific Y1 receptor agonist. Proc Natl Acad Sci U S A. 1990 Jan;87(1):182–186. doi: 10.1073/pnas.87.1.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerard N. P., Eddy R. L., Jr, Shows T. B., Gerard C. The human neurokinin A (substance K) receptor. Molecular cloning of the gene, chromosome localization, and isolation of cDNA from tracheal and gastric tissues. J Biol Chem. 1990 Nov 25;265(33):20455–20462. [PubMed] [Google Scholar]
- Glover I. D., Barlow D. J., Pitts J. E., Wood S. P., Tickle I. J., Blundell T. L., Tatemoto K., Kimmel J. R., Wollmer A., Strassburger W. Conformational studies on the pancreatic polypeptide hormone family. Eur J Biochem. 1984 Jul 16;142(2):379–385. doi: 10.1111/j.1432-1033.1984.tb08298.x. [DOI] [PubMed] [Google Scholar]
- Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
- Heilig M., Widerlöv E. Neuropeptide Y: an overview of central distribution, functional aspects, and possible involvement in neuropsychiatric illnesses. Acta Psychiatr Scand. 1990 Aug;82(2):95–114. doi: 10.1111/j.1600-0447.1990.tb01366.x. [DOI] [PubMed] [Google Scholar]
- Hinson J., Rauh C., Coupet J. Neuropeptide Y stimulates inositol phospholipid hydrolysis in rat brain miniprisms. Brain Res. 1988 Apr 19;446(2):379–382. doi: 10.1016/0006-8993(88)90898-0. [DOI] [PubMed] [Google Scholar]
- 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]
- Mihara S., Shigeri Y., Fujimoto M. Neuropeptide Y-induced intracellular Ca2+ increases in vascular smooth muscle cells. FEBS Lett. 1989 Dec 18;259(1):79–82. doi: 10.1016/0014-5793(89)81499-1. [DOI] [PubMed] [Google Scholar]
- Potter E. K., Fuhlendorff J., Schwartz T. W. [Pro34]neuropeptide Y selectively identifies postjunctional-mediated actions of neuropeptide Y in vivo in rats and dogs. Eur J Pharmacol. 1991 Jan 25;193(1):15–19. doi: 10.1016/0014-2999(91)90194-u. [DOI] [PubMed] [Google Scholar]
- Sheikh S. P., O'Hare M. M., Tortora O., Schwartz T. W. Binding of monoiodinated neuropeptide Y to hippocampal membranes and human neuroblastoma cell lines. J Biol Chem. 1989 Apr 25;264(12):6648–6654. [PubMed] [Google Scholar]
- Shigeri Y., Mihara S., Fujimoto M. Neuropeptide Y receptor in vascular smooth muscle. J Neurochem. 1991 Mar;56(3):852–859. doi: 10.1111/j.1471-4159.1991.tb02001.x. [DOI] [PubMed] [Google Scholar]
- Strosberg A. D. Structure/function relationship of proteins belonging to the family of receptors coupled to GTP-binding proteins. Eur J Biochem. 1991 Feb 26;196(1):1–10. doi: 10.1111/j.1432-1033.1991.tb15778.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Wahlestedt C., Håkanson R., Vaz C. A., Zukowska-Grojec Z. Norepinephrine and neuropeptide Y: vasoconstrictor cooperation in vivo and in vitro. Am J Physiol. 1990 Mar;258(3 Pt 2):R736–R742. doi: 10.1152/ajpregu.1990.258.3.R736. [DOI] [PubMed] [Google Scholar]
- Wahlestedt C., Yanaihara N., Håkanson R. Evidence for different pre-and post-junctional receptors for neuropeptide Y and related peptides. Regul Pept. 1986 Feb;13(3-4):307–318. doi: 10.1016/0167-0115(86)90048-0. [DOI] [PubMed] [Google Scholar]