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UDP is an antagonist at the hP2Y14 receptor
Author(s) -
Fricks Ingrid P.,
Maddileti Savitri,
Lazarowski Eduardo R.,
Nicholas Robert A.,
Jacobson Kenneth A.,
Harden T. Kendall
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a424-c
Subject(s) - g protein coupled receptor , antagonist , competitive antagonist , receptor , agonist , g protein , biology , chemistry , microbiology and biotechnology , biochemistry
The P2Y14‐R is the eighth identified member of the P2Y‐R family of G protein‐coupled receptors (GPCRs) and is uniquely activated by nucleotide‐sugars. With the goal of developing novel high affinity ligands, we sought to identify an antagonist for the P2Y14‐R. We applied a cell‐based assay for the P2Y14‐R using a chimeric Gα subunit that allows Gαi‐coupled GPCRs to signal through phospholipase C. Uridine diphosphate (UDP) was identified as an antagonist at the hP2Y14‐R. Schild analysis confirmed the antagonism was competitive (pK B = 7.28). Antagonist activity by UDP was selective for the hP2Y14‐R among all eight human P2Y receptors. To determine whether UDP was also a competitive antagonist at other P2Y14‐R orthologs, we cloned the rat P2Y14‐R and examined the activity of UDP at this receptor. In contrast to its action at the human P2Y14‐R, UDP was a potent, full agonist at the rat P2Y14‐R with an EC50 of 0.35 μM. Discovery of high affinity ligands for the P2Y14‐R will provide important tools for expanding our knowledge of physiological roles played by this receptor.