A structure-activity analysis of the cloned rat and human Y4 receptors for pancreatic polypeptide.
We cloned and expressed the rat Y4 receptor for pancreatic polypeptide (PP). Structure-activity profiles derived from 125I-PP binding assays and [cAMP] radioimmunoassays reveal a selective receptor interaction with rat PP vs. neuropeptide Y (NPY) or peptide YY (PYY). Rat and human Y4 receptor clones share 75% amino acid identity. Based on [cAMP] radioimmunoassay, the human Y4 receptor exhibits a less selective interaction with rat PP vs. NPY or PYY and a greater dependence on N-terminal PP residues, relative to rat Y4. Differences in sequence and structure-activity profiles suggest the rat be used with caution to model human Y4 receptor function.
Walker
M W
MW
Synpatic Pharmaceutical Corporation, Paramus, NJ 07652, USA.
Smith
K E
KE
Bard
J
J
Vaysse
P J
PJ
Gerald
C
C
Daouti
S
S
Weinshank
R L
RL
Branchek
T A
TA
D000818:Animals; D003001:Cloning, Molecular; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010191:Pancreatic Polypeptide; D011869:Radioligand Assay; D051381:Rats; D011964:Receptors, Gastrointestinal Hormone / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D011964:Receptors, Gastrointestinal Hormone; C029438:receptors, pancreatic polypeptide-specific; D010191:Pancreatic Polypeptide