Pyroglutamylated RFamide peptide receptor (QRFPR)

Pyroglutamylated RFamide peptide receptor (QRFPR, also known as GPR103) is a class A G protein-coupled receptor that binds the peptide ligand QRFP (also known as 26RFa or P518), which features a C-terminal RF-amide motif[1][2][3][4]. QRFPR is expressed in the brain (notably the hypothalamus) and peripheral tissues such as adrenal gland and heart[1][4]. Activation by QRFP or 26RFa couples the receptor to Gq and Gi/o proteins, leading to downstream signaling involved in energy homeostasis, appetite stimulation, sleep regulation, cardiovascular function, and bone formation[1][2][4]. QRFP and its receptor are conserved across vertebrates, indicating fundamental roles in physiology[1][3]. Dysregulation of this system is implicated in metabolic diseases such as obesity, diabetes, cardiovascular disorders, and appetite-related disorders[1][2][4]. QRFPR antagonists are under investigation as potential therapies for metabolic syndrome, obesity, and related conditions due to their ability to suppress orexigenic (appetite-stimulating) activity[1]. Additionally, QRFP may serve as a biomarker for specialized neurons (Q-neurons) and specific states of metabolic suppression or hypothermia, with ongoing research into therapeutic modulation and synthetic ligand design[1].

Other names

Orexigenic neuropeptide QRFPQRF-amideQRFP26RFaP518prepro-26RFaprepro-QRFPPyroglutamylated arginine-phenylalanine-amide peptideNeuropeptide RF-amideP518 precursor proteinRF(Arg-Phe)amide family 26 amino acid peptide (P518)

G protein-coupled receptor antagonism (blocking QRFP-induced activation of GPR103); Inverse agonism (suggested for anorexic agents)