Expression cloning and pharmacological characterization of a human hippocampal neuropeptide Y/peptide YY Y2 receptor subtype.
The pancreatic polypeptide family includes neuropeptide Y (NPY), one of the most abundant neuropeptides in the mammalian nervous system, as well as peptide YY (PYY) and pancreatic polypeptide (PP). This peptide family is involved in numerous physiological processes such as memory, pain, blood pressure, appetite, anxiety, and circadian rhythm. Of the multiple Y-type receptors proposed for PP family members, only the Y1 subtype was cloned previously. We now report the isolation of a human Y2 (hhY2) receptor cDNA by expression cloning from a human hippocampal cDNA library, using a 125I-PYY binding assay. hhY2 cDNA encodes a predicted protein of 381 amino acids with low amino acid identity to the human Y1 receptor (31% overall; 41% transmembrane). 125I-PYY binding to transiently expressed hY2 receptors was saturable (pKd = 10.17) and displaceable by human PP family members in rank order: PYY (pKi = 9.47) approximately NPY (pKi = 9.27) >> PP (pKi < 6) and by peptide analogs: NPY2-36 (pKi = 8.80) approximately NPY13-36 (pKi = 8.55) approximately C2-NPY (pKi = 8.54) > NPY26-36 (pKi = 6.51) approximately [Leu31,Pro34]NPY (pKi = 6.23). Human PYY decreased [cAMP] and increased intracellular [Ca2+] in hY2-transfected 293 cells.
Gerald
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Synaptic Pharmaceutical Corporation, Paramus, New Jersey 07652, USA.
Walker
M W
MW
Vaysse
P J
PJ
He
C
C
Branchek
T A
TA
Weinshank
R L
RL
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D010191:Pancreatic Polypeptide / Q000378:metabolism; D019894:Peptide YY; D010455:Peptides / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D010455:Peptides; D011964:Receptors, Gastrointestinal Hormone; D017476:Receptors, Neuropeptide Y; C082172:peptide YY receptor; C029438:receptors, pancreatic polypeptide-specific; D019894:Peptide YY; D010191:Pancreatic Polypeptide