Interaction of NPY compounds with the rat glucocorticoid-induced receptor (GIR) reveals similarity to the NPY-Y2 receptor.
The rat glucocorticoid-induced receptor (rGIR) is an orphan G protein-coupled receptor awaiting pharmacological characterization. Among known receptors, rGIR exhibits highest sequence similarity to the neuropeptide Y (NPY)-Y(2) receptor (38-40%). The pharmacological profile of rGIR was investigated using (125)I-PYY(3-36), a Y(2)-preferring radioligand and several NPY analogs. rGIR displayed a similar displacement profile as reported for the Y(2) receptor, in that the Y(2)-selective C terminus fragments of NPY and PYY (NPY(3-36) and PYY(3-36)) showed high affinity binding and activation of rGIR (low nanomolar range). The rank order potency for displacement was NPY(3-36)>PYY(3-36)=NPY>NPY(13-36)>Ac, Leu NPY(24-36)>[D-Trp(32)]-NPY>Leu(31), Pro(34)-NPY=hPP. NPY and Y(2)-selective agonists NPY(3-36) and PYY(3-36) led to significant activation of (35)S-GTPgammaS binding to rGIR transfected cells. BIIE0246, a specific Y(2) antagonist, displaced (125)I-PYY(3-36) binding to rGIR with high affinity (95nM). Activation of (35)S-GTPgammaS binding by Y(2)-selective agonist in rGIR transfected cells was also completely abolished by BIIE0246. Our data report, for the first time, an interaction of NPY ligands with rGIR expressed in vitro, and indicate similarities between GIR and the NPY-Y(2) receptor.
Sah
Renu
R
Department of Psychiatry, University of Cincinnati Medical Center, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
Parker
Steven L
SL
Sheriff
Sulaiman
S
Eaton
Katherine
K
Balasubramaniam
Ambikaipakan
A
Sallee
Floyd R
FR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D017931:DNA Primers; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000187:drug effects*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; C501985:Gpr83 protein, rat; D009478:Neuropeptide Y; D043562:Receptors, G-Protein-Coupled; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor