FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54.
We have isolated and determined the coding sequences of human and mouse orthologs of the rat orphan G-protein-coupled receptor GPR54. Mouse and rat GPR54 are nearly 95% identical to each other, and both are approximately 85% identical to human GPR54 at the amino acid level. Screening of agonists for GPR54 identified several invertebrate neuropeptides of the RFamide and RWamide family that were able to activate GPR54 at microM range through the G(alpha)q pathway. Substitution analysis showed that the C-terminal optimal sequence of GPR54-activating peptides is Gly-Leu-Arg-Trp-NH2. Northern analysis of human GPR54 detected expression in several peripheral tissues and many regions of the central nervous system.
Clements
M K
MK
Department of Pharmacology, WP26A-3000, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
McDonald
T P
TP
Wang
R
R
Xie
G
G
O'Dowd
B F
BF
George
S R
SR
Austin
C P
CP
Liu
Q
Q
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D019835:FMRFamide / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; C118688:KISS1R protein, human; C492248:Kiss1r protein, mouse; C492247:Kiss1r protein, rat; D009479:Neuropeptides; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide; D019835:FMRFamide