The Arg–Phe‐amide peptide 26RFa/glutamine RF‐amide peptide and its receptor: IUPHAR Review 24

Abstract

This article, contributed by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee for the QRFP receptor, confirms the existing nomenclature for this receptor, and reviews our current understanding of its structure, pharmacology and functions, and likely physiological roles in health and disease. More information on this receptor can be found in the Concise Guide to PHARMACOLOGY The RFamide neuropeptide 26RFa was first isolated from the brain of the European green frog on the basis of cross-reactivity with antibodies raised against bovine neuropeptide FF (NPFF). 26RFa and its N-terminally extended form glutamine RF-amide peptide (QRFP) have been identified as cognate ligands of the former orphan receptor GPR103, now renamed glutamine RF-amide peptide receptor (QRFP receptor). The 26RFa/QRFP precursor has been characterized in various mammalian and non-mammalian species. In the brain of mammals, including humans, 26RFa/QRFP mRNA is almost exclusively expressed in hypothalamic nuclei. The 26RFa/QRFP transcript is also present in various organs especially in endocrine glands. While humans express only one QRFP receptor, two isoforms are present in rodents. The QRFP receptor genes are widely expressed in the CNS and in peripheral tissues, notably in bone, heart, kidney, pancreas and testis. Structure-activity relationship studies have led to the identification of low MW peptidergic agonists and antagonists of QRFP receptor. Concurrently, several selective non-peptidic antagonists have been designed from high-throughput screening hit optimization. Consistent with the widespread distribution of QRFP receptor mRNA and 26RFa binding sites, 26RFa/QRFP exerts a large range of biological activities, notably in the control of energy homeostasis, bone formation and nociception that are mediated by QRFP receptor or NPFF2. The present report reviews the current knowledge concerning the 26RFa/QRFP-QRFP receptor system and discusses the potential use of selective QRFP receptor ligands for therapeutic applications.

Evolution of neuropeptide signalling systems

“…The peptide QRFP begins with the amino acid glutamine (Q) and ends with RFamide, thereby resembling other RFamide peptides and the RYamide peptides NPY and PYY ( Elphick and Mirabeau, 2014 ; Leprince et al, 2017 ). QRFP was discovered independently in frog and mammalian brain, and a single gene has been found throughout the vertebrates ( Leprince et al, 2017 ). In the hypothalamus, QRFP can potently stimulate food intake ( Leprince et al, 2017 ).…”

“…QRFP was discovered independently in frog and mammalian brain, and a single gene has been found throughout the vertebrates ( Leprince et al, 2017 ). In the hypothalamus, QRFP can potently stimulate food intake ( Leprince et al, 2017 ). A single QRFP receptor has been described in mammals ( Fig.…”

Glucose homeostasis is impaired in mice deficient in the neuropeptide 26RFa (QRFP)

“…26RFa (also referred to as pyroglutamyl RFamide peptide (QRFP)) is a hypothalamic neuropeptide discovered concurrently by us and others 10–12. 26RFa has been characterized in all vertebrate phyla including human,13 14 and identified as the cognate ligand of the human orphan G protein-coupled receptor, GPR103 11–13 15 16. Neuroanatomical observations revealed that 26RFa-expressing and GPR103-expressing neurons are primarily localized in hypothalamic nuclei involved in the control of feeding behavior 10 11 15 17 18.…”

Glucose homeostasis is impaired in mice deficient for the neuropeptide 26RFa (QRFP)

“…26RFa (also referred to as QRFP) is a hypothalamic neuropeptide discovered concurrently by us and others (10-12). 26RFa has been characterized in all vertebrate phyla including human (13, 14), and identified as the cognate ligand of the human orphan G protein-coupled receptor, GPR103 (11-13,15, 16). Neuroanatomical observations revealed that 26RFa- and GPR103-expressing neurons are primarily localized in hypothalamic nuclei involved in the control of feeding behaviour (10,11,15,17,18).…”