Cloning and Functional Expression of a Human Y4 Subtype Receptor for Pancreatic Polypeptide, Neuropeptide Y, and Peptide YY ()

• Published in: The Journal of biological chemistry Vol. 270; no. 45; pp. 26762 - 26765
• Main Authors: Bard, Jonathan A., Walker, Mary W., Branchek, Theresa A., Weinshank, Richard L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10-11-1995; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Cloning, Molecular; DNA Primers - genetics; Female; Gene Expression; Humans; In Vitro Techniques; Male; Mice; Molecular Sequence Data; Neuropeptide Y - metabolism; Pancreatic Polypeptide - metabolism; Peptide YY; Peptides - metabolism; Rats; Receptors, Gastrointestinal Hormone - classification; Receptors, Gastrointestinal Hormone - genetics; Receptors, Gastrointestinal Hormone - metabolism; Receptors, Neuropeptide Y - classification; Receptors, Neuropeptide Y - genetics; Receptors, Neuropeptide Y - metabolism; Sequence Homology, Amino Acid
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.45.26762

The pancreatic polypeptide family includes pancreatic polypeptide (PP), neuropeptide Y (NPY), and peptide YY (PYY). Members of the PP family regulate numerous physiological processes, including appetite, gastrointestinal transit, anxiety, and blood pressure. Of the multiple Y-type receptors proposed for PP family members, only the Y1 subtype has been cloned previously. We now report the cloning of an additional Y-type receptor, designated Y4, by homology screening of a human placental genomic library with transmembrane (TM) probes derived from the rat Y1 gene. The Y4 genomic clone encodes a predicted protein of 375 amino acids that is most homologous to Y1 receptors from human, rat, and mouse (42% overall; 55% in TM). 125I-PYY binding to transiently expressed Y4 receptors was saturable (pKd = 9.89) and displaceable by human PP family derivatives: PP (pKi = 10.25) ~ PP2-36 (pKi = 10.06) > PYY (pKi = 9.06) ~ [Leu31,Pro34]NPY (pKi = 8.95) > NPY (pKi = 8.68) > PP13-36 (pKi = 7.13) > PP31-36 (pKi = 6.46) > PP31-36 free acid (pKi < 5). Human PP decreased [cAMP] and increased intracellular [Ca2+] in Y4-transfected LMTK- cells. Y4 mRNA was detected by reverse transcriptase-polymerase chain reaction in human brain, coronary artery, and ileum, suggesting potential roles for Y4 receptors in central nervous system, cardiovascular, and gastrointestinal function.