Cloning and functional expression of a human neuropeptide Y/peptide YY receptor of the Y1 type

D. Larhammar, A. G. Blomqvist, F. Yee, E. Jazin, H. Yoo, C. Wahlestedt

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378 Scopus citations

Abstract

Neuropeptide Y (NPY) and peptide YY (PYY) are structurally related peptides that primarily function as neurotransmitter and gastrointestinal hormone, respectively. Previous functional and binding data have indicated the existence of at least three distinct receptor types, Y1, Y2, and Y3, for NPY and/or PYY in mammals. We describe here a human Y1 cDNA clone, hY1-5, isolated from a fetal brain library. The human Y1 receptor consists of 384 amino acids and has seven putative transmembrane domains like other members of the G-protein-coupled superfamily of receptors. In the region spanning the transmembrane domains, the Y1 receptor displays 29% sequence identity to human tachykinin receptors, but it only shows 21% and 23% homology with proposed bovine (LCR1) and Drosophila (PR4) NPY receptor clones, respectively. Northern blot analysis of a human neuroblastoma cell line, SK-N-MC, previously used by many investigators as a model system for studies on the Y1 receptor, revealed a single 3.5-kilobase mRNA species. 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. When expressed in COS1 cells, hY1-5 conferred specific 125I-PYY binding sites with displacement patterns characteristic of the Y1 receptor, i.e. PYY ≥ NPY ≥ [Leu31,Pro34]NPY ≫ NPY2-36 > C2NPY > pancreatic polypeptide > NPY13-36 > NPY18-36. Moreover, in the Y1 receptor-transfected COS1 cells, but not in type 1 angiotensin II receptor-transfected control cells, NPY and PYY accelerated 45Ca2+ influx and inhibited forskolin-stimulated cAMP accumulation, both phenomena being characteristic of the mammalian Y1 receptor.

Original languageEnglish (US)
Pages (from-to)10935-10938
Number of pages4
JournalJournal of Biological Chemistry
Volume267
Issue number16
StatePublished - 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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