Npffr1, also known as GPR147, is the seven-transmembrane G protein-coupled receptor for neuropeptide FF (NPFF) and gonadotropin-inhibitory hormone (GnIH) [1]. It inhibits cAMP production and is involved in multiple physiological processes such as cardiovascular regulation, nociception, and reproduction [1,4,5]. The NPFF-Npffr1 signaling pathway is also potentially related to the regulation of energy homeostasis and blood pressure [4,6,7]. Genetic models like knockout mice can be valuable for studying its functions.

In male mouse models of acute fentanyl-induced analgesia and hyperalgesia, Npffr1 knockout (npffr1-/-) mice showed a marked reversal of fentanyl-induced hyperalgesia, indicating that Npffr1 plays a role in opioid-induced hyperalgesia [2]. In female rats, the selective Npffr1 antagonist GJ14 blocked the RFRP-3-induced increase in prolactin secretion, suggesting that RFRP-3 binds to Npffr1 to stimulate prolactin release [3].

In conclusion, Npffr1 is involved in various physiological functions including pain modulation, prolactin secretion regulation, and potentially in blood pressure and energy homeostasis. The use of npffr1-/-mouse models has been crucial in revealing its role in opioid-induced hyperalgesia, providing insights into the underlying mechanisms and potential therapeutic targets for pain-related and reproductive-related diseases [2,3].

References:

1. 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/

2. 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/

3. 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/

4. 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/

5. Nguyen, Thuy, Marusich, Julie, Li, Jun-Xu, Zhang, Yanan. 2020. Neuropeptide FF and Its Receptors: Therapeutic Applications and Ligand Development. In Journal of medicinal chemistry, 63, 12387-12402. doi:10.1021/acs.jmedchem.0c00643. https://pubmed.ncbi.nlm.nih.gov/32673481/

6. 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/

7. Koller, Julia, Herzog, Herbert, Zhang, Lei. 2021. The distribution of Neuropeptide FF and Neuropeptide VF in central and peripheral tissues and their role in energy homeostasis control. In Neuropeptides, 90, 102198. doi:10.1016/j.npep.2021.102198. https://pubmed.ncbi.nlm.nih.gov/34534716/