Recent advances in mammalian RFamide peptides: the discovery and functional analyses of PrRP, RFRPs and QRFP.
Since the first discovery of a peptide with RFamide structure at its C-terminus (i.e., an RFamide peptide) from an invertebrate in 1977, numerous studies on RFamide peptides have been conducted, and a variety have been identified in various phyla throughout the animal kingdom. The first reported mammalian RFamide peptides were neuropeptide FF (NPFF) and neuropeptide AF (NPAF) in 1985. However, for many years after this, no new novel RFamide peptides were identified in mammals. A breakthrough in discovering mammalian RFamide peptides was made possible by reverse pharmacology on the basis of orphan G protein-coupled receptor (GPCR) research. The first report of an RFamide peptide identified from orphan GPCR research was prolactin (PRL)-releasing peptide (PrRP) in 1998. To date, a total of five RFamide peptide genes have been discovered in mammals. Orphan GPCR research has contributed considerably to the identification of these peptides and their receptor genes. This paper examines these mammalian RFamide peptides focusing especially on PrRP, RFamide-related peptides (RFRPs) and, the most recently identified, pyroglutamylated RFamide peptide (QRFP), the discovery of all of which the authors were at least partly involved in. We review here the strategies employed for the identification of these peptides and examine their characteristics, tissue distribution, receptors and functions.
Fukusumi
Shoji
S
Frontier Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., Wadai 10, Tsukuba-shi, Ibaraki 300-4293, Japan.
Fujii
Ryo
R
Hinuma
Shuji
S
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009479:Neuropeptides / Q000502:physiology*; D010455:Peptides / Q000302:isolation & purification / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000737:chemistry; D018013:Receptors, Neuropeptide / Q000032:analysis; D013312:Stress, Physiological / Q000503:physiopathology; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*; D014018:Tissue Distribution
D036341:Intercellular Signaling Peptides and Proteins; D009479:Neuropeptides; C112345:PRLHR protein, human; D010455:Peptides; C511787:QRFP peptide; C416987:RFamide peptide; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor; D013973:Thyrotropin-Releasing Hormone