The cloned rat pancreatic polypeptide receptor exhibits profound differences to the orthologous receptor.
Pancreatic polypeptide (PP) is produced in the islets of Langerhans and released in response to meals. It belongs to a family of peptides that also includes neuropeptide Y and peptide YY. In the present communication, we describe a rat receptor with high affinity for PP, therefore named PP1. Clones for the PP1 receptor were obtained by PCR using sequence information for the neuropeptide Y receptor Y1 from several species. The PP1 receptor has 46% overall amino acid sequence identity to the rat Y1 receptor and 56% identity in the transmembrane regions. The PP1 receptor displays a pharmacological profile that is distinct from previously described neuropeptide Y-family receptors. In competition with iodinated bovine PP, it binds rat PP with an affinity (K(i)) of 0.017 nM, while the affinities for peptide YY and neuropeptide Y are substantially lower with K(i) values of 162 and 192 nM, respectively. In stably transfected CHO cells, the PP1 receptor inhibits forskolin-stimulated cAMP synthesis. Northern blot hybridizations to a panel of mRNAs detected transcripts in testis and lung. A faint band was seen in colon and total brain. In contrast, the human receptor is expressed primarily in colon and small intestine. Whereas rat and human PP1 bind PP with the same affinity, the rat receptor has much lower affinity than its human ortholog for peptide YY and neuropeptide Y. Interestingly, the amino acid sequence identity between rat and human PP1 is only 75%. Thus, the sequence, the tissue distribution, and the binding profile of the PP1 receptor differ considerably between rat and human.
Lundell
I
I
Department of Medical Pharmacology, Uppsala University, Sweden.
Statnick
M A
MA
Johnson
D
D
Schober
D A
DA
Starbäck
P
P
Gehlert
D R
DR
Larhammar
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002417:Cattle; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D010191:Pancreatic Polypeptide / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014018:Tissue Distribution; D014162:Transfection
D017931:DNA Primers; D011964:Receptors, Gastrointestinal Hormone; D011994:Recombinant Proteins; C029438:receptors, pancreatic polypeptide-specific; D010191:Pancreatic Polypeptide