Npffr1, also known as gonadotropin-inhibitory hormone receptor (GnIHR) and G protein-coupled receptor 147 (GPR147), is a seven-transmembrane G protein-coupled receptor. It binds neuropeptide FF (NPFF), RFamide-related peptide 3 (RFRP-3) and kisspeptin (Kp). Npffr1 is involved in multiple physiological processes, including pain modulation, regulation of prolactin secretion, and blood pressure control [2,3,4,5]. Genetic models, such as knockout mice, are valuable for studying its functions.

In npffr1-/- mice, fentanyl-induced hyperalgesia was markedly reversed, indicating a role of Npffr1 in opioid-induced hyperalgesia [1]. Also, the unselective Npffr1 antagonist RF9 and the selective antagonist GJ14 could prevent the responses of prolactin (PRL) and luteinizing hormone (LH) secretion induced by Kp and RFRP-3, revealing the role of Npffr1 in the control of PRL secretion [2].

In conclusion, Npffr1 plays crucial roles in pain modulation, particularly in opioid-induced hyperalgesia, and in the regulation of prolactin secretion. The use of Npffr1 knockout mouse models has significantly contributed to understanding its functions in these specific biological processes, providing insights into potential therapeutic targets for related conditions.

References:

1. Chen, Dan, Zhang, Mengna, Zhang, Qinqin, Xu, Biao, Fang, Quan. 2024. The blockade of neuropeptide FF receptor 1 and 2 differentially contributed to the modulating effects on fentanyl-induced analgesia and hyperalgesia in mice. In European journal of pharmacology, 969, 176457. doi:10.1016/j.ejphar.2024.176457. https://pubmed.ncbi.nlm.nih.gov/38395375/

2. Aquino, Nayara S S, Mansano, Naira S, Vieira, Fernanda A S, Reis, Adelina M, Szawka, Raphael E. . RFamide-related Peptide 3 Signaling via Neuropeptide FF Receptor Stimulates Prolactin Secretion in Female Rats. In Endocrinology, 164, . doi:10.1210/endocr/bqad102. https://pubmed.ncbi.nlm.nih.gov/37403228/

3. Ubuka, Takayoshi, Tsutsui, Kazuyoshi. 2014. Evolution of gonadotropin-inhibitory hormone receptor and its ligand. In General and comparative endocrinology, 209, 148-61. doi:10.1016/j.ygcen.2014.09.002. https://pubmed.ncbi.nlm.nih.gov/25220854/

4. Lee, Hewang, Amatya, Bibhas, Villar, Van Anthony M, Hao, Ling, Jose, Pedro A. 2024. Renal autocrine neuropeptide FF (NPFF) signaling regulates blood pressure. In Scientific reports, 14, 15407. doi:10.1038/s41598-024-64484-9. https://pubmed.ncbi.nlm.nih.gov/38965251/

5. Lee, Hewang, Feranil, Jun B, Jose, Pedro A. 2024. An Overview on Renal and Central Regulation of Blood Pressure by Neuropeptide FF and Its Receptors. In International journal of molecular sciences, 25, . doi:10.3390/ijms252413284. https://pubmed.ncbi.nlm.nih.gov/39769048/