Neuropeptide FF receptor 1 (NPFFR1)

Neuropeptide FF receptor 1 (NPFFR1), also known as GPR147, is a G protein-coupled receptor highly expressed in the central nervous system, particularly in the hypothalamus and limbic system[3][4]. It binds RFamide peptides, especially the gonadotropin-inhibitory hormone (GnIH, RFRP peptide family), and participates in the regulation of reproductive hormone release and modulation of opioid system function[1][4][5]. NPFFR1 activation is associated with inhibition of adenylyl cyclase and downstream signaling cascades, affecting neuroendocrine processes and pain modulation. In humans, NPFFR1 is implicated in pain regulation, tolerance to opioid analgesia, cardiovascular function, anxiety, and other CNS-driven processes, making it a focus of therapeutic interest, particularly for chronic pain and opioid-induced side effect modulation[4][2][3]. Selective antagonists (such as RF9 and hederagenin) and peptide agonists are tool compounds used in NPFFR1-targeted research[2][3][6].

Other names

Neuropeptide FF receptor 1NPFFR1GPR147NPFF1OT7T022NPFF1R1G-protein coupled receptor 147RFamide-related peptide receptor OT7T022

Agonists (such as neuropeptide FF, AF, SF) activate NPFFR1, leading to inhibition of adenylyl cyclase via Gi-coupling, modulation of ion channels, and regulation of downstream MAPK and ERK pathways[5]. - Antagonists (like RF9 and hederagenin) block NPFFR1 activation, interfering with NPFF-mediated antiopioid, pronociceptive, and neuroendocrine-modulating effects[2][6][4][5].