Identification and characterization of two G protein-coupled receptors for neuropeptide FF.
The central nervous system octapeptide, neuropeptide FF (NPFF), is believed to play a role in pain modulation and opiate tolerance. Two G protein-coupled receptors, NPFF1 and NPFF2, were isolated from human and rat central nervous system tissues. NPFF specifically bound to NPFF1 (K(d) = 1.13 nm) and NPFF2 (K(d) = 0.37 nm), and both receptors were activated by NPFF in a variety of heterologous expression systems. The localization of mRNA and binding sites of these receptors in the dorsal horn of the spinal cord, the lateral hypothalamus, the spinal trigeminal nuclei, and the thalamic nuclei supports a role for NPFF in pain modulation. Among the receptors with the highest amino acid sequence homology to NPFF1 and NPFF2 are members of the orexin, NPY, and cholecystokinin families, which have been implicated in feeding. These similarities together with the finding that BIBP3226, an anorexigenic Y1 receptor ligand, also binds to NPFF1 suggest a potential role for NPFF1 in feeding. The identification of NPFF1 and NPFF2 will help delineate their roles in these and other physiological functions.
Bonini
J A
JA
Synaptic Pharmaceutical Corporation, Paramus, New Jersey 07652, USA. jbonini@synapticcorp.com
Jones
K A
KA
Adham
N
N
Forray
C
C
Artymyshyn
R
R
Durkin
M M
MM
Smith
K E
KE
Tamm
J A
JA
Boteju
L W
LW
Lakhlani
P P
PP
Raddatz
R
R
Yao
W J
WJ
Ogozalek
K L
KL
Boyle
N
N
Kouranova
E V
EV
Quan
Y
Y
Vaysse
P J
PJ
Wetzel
J M
JM
Branchek
T A
TA
Gerald
C
C
Borowsky
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004594:Electrophysiology; D015723:Gene Library; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D009865:Oocytes; D010716:Phosphatidylinositols / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014981:Xenopus
C092926:BIBP 3226; D018076:DNA, Complementary; D008024:Ligands; D009842:Oligopeptides; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor; D001120:Arginine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D000242:Cyclic AMP; D002118:Calcium