Cloning and functional expression of a human neuropeptide Y/peptide YY receptor of the Y1 type.
1992; Elsevier BV; Volume: 267; Issue: 16 Linguagem: Inglês
10.1016/s0021-9258(19)49854-2
ISSN1083-351X
AutoresDan Larhammar, Anders Blomqvist, Frances Yee, Elena Jazin, H. Yoo, C Wahlested,
Tópico(s)Chemical Synthesis and Analysis
ResumoNeuropeptide 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 Y 1 cDNA clone, hY 1-6, isolated from a fetal brain library.The human Y 1 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 (LCRl) 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 Y 1 receptor, revealed a single 3.6-kilobase mRNA species.Reverse transcriptase-polymerase chain reaction analysis indicated expression also in human cultured vascular smooth muscle cells, supporting the view that the Y 1 receptor is associated with NPYJPYY-evoked vasoconstriction.When expressed in COSl cells, hY1-5 conferred specific '*'I-PYY binding sites with displacement patterns characteristic of the Y 1 receptor, i.e.PYY 2 NPY 2 [ L e ~~' , p r o ~~l N P Y >> NPY2-36 > C2NPY > pancreatic polypeptide > NPY 13-36 > NPY 18-36.Moreover, in the Y 1 receptor-transfected COSl cells, but not in type 1 angiotensin I1 receptor-transfected control cells, NPY and PYY accelerated 4SCa2+ influx and inhibited forskolin-stimulated CAMP accumulation,
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