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 ort hologs of the rat orphan G-protein-coupled receptor GPR54. Mouse and rat GP R54 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 RWa mide family that were able to activate GPR54 at muM range through the G(alp haq) pathway. Substitution analysis showed that the C-terminal optimal sequ ence 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. (C) 2001 Academic Press.