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(Received for publication, August 18, 1995; and in revised form, September 5, 1995) 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).
Volume 270,
Number 45,
Issue of November 10, 1995 pp. 26762-26765
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
I-PYY binding to
transiently expressed Y4 receptors was saturable (pK
= 9.89) and displaceable by human PP family
derivatives: PP (pK
= 10.25)
PP
(pK
=
10.06) > PYY (pK
= 9.06)
[Leu
,Pro
]NPY (pK
= 8.95) > NPY (pK
= 8.68) > PP
(pK
= 7.13) >
PP
(pK
=
6.46) > PP
free acid (pK
< 5). Human PP decreased [cAMP] and increased
intracellular [Ca
] 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.
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Y. Hu, B. T. Bloomquist, L. J. Cornfield, L. B. DeCarr, J. R. Flores-Riveros, L. Friedman, P. Jiang, L. Lewis-Higgins, Y. Sadlowski, J. Schaefer, et al. Identification of a Novel Hypothalamic Neuropeptide Y Receptor Associated with Feeding Behavior J. Biol. Chem., October 18, 1996; 271(42): 26315 - 26319. [Abstract] [Full Text] [PDF]
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