NPFF

Neuropeptide FF-amide peptide precursor
Identifiers
Symbols	NPFF; FMRFAL
External IDs	OMIM: 604643 MGI: 1891708 HomoloGene: 48236 GeneCards: NPFF Gene
Gene Ontology Molecular function • receptor binding • neuropeptide hormone activity Cellular component • extracellular region • extracellular region • soluble fraction Biological process • neuropeptide signaling pathway • synaptic transmission Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8620	54615
Ensembl	ENSG00000139574	ENSMUSG00000023052
UniProt	O15130	Q9WVA8
RefSeq (mRNA)	NM_003717	NM_018787
RefSeq (protein)	NP_003708	NP_061257.1
Location (UCSC)	Chr 12: 53.9 – 53.9 Mb	Chr 15: 102.35 – 102.36 Mb
PubMed search	[1]	[2]

NPFF Neuropeptide FF (FLFQPQRFa) is a mammalian amidated neuropeptide originally isolated from bovine brain and characterized as a pain-modulating peptide, with anti-opioid activity on morphine-induced analgesia.

In humans, Neuropeptide FF peptides are encoded by the NPFF gene. Two genes encoding two different receptors (NPFF1 and NPFF2)and two precursors (NPFFA and NPFFB) have been cloned in several mammalian species.^[1][2]

Neuropeptide FF (NPFF) and RFamide related peptides issued from two precursors interact with good affinity with two subtypes of G protein-coupled receptors, namely NPFF1 and NPFF2 subtypes and are involved in several physiological functions such as cardiovascular regulation, hormonal control, body temperature homeostasis and pain modulation.^[2]

Processing of the NPFFA precursor at basic proteolytic sites should generate a NPFF-containing peptide with three additional N-terminal amino acids different between species, and a NPSF (SLAAPQRFa)-containing peptide, the length of which depends on the species. NPFFB, identified as a precursor for RFamide-related peptides (RFR-P, also called GnIH for Gonadotropin inhibitory hormone), contains a LPLRFa-containing peptide and a peptide sharing with NPFF the same C-terminal PQRFamide motif, such as NPVF (VPNLPQRFa) in human.

NPFF and opioid systems have been shown to interact at several levels, from animal behavior to receptor molecules. Nociception is the physiological function in which this interaction has been the most extensively studied but reward, locomotion, feeding and intestinal motility are also affected. Endogenous opioids are necessary for the analgesic properties of spinally injected NPFF while endogenous NPFF peptides are involved in the process of analgesic tolerance/hyperalgesia induced by chronic opioid treatment.

References

1. ^ Perry SJ, Yi-Kung Huang E, Cronk D, Bagust J, Sharma R, Walker RJ, Wilson S, Burke JF (Aug 1997). "A human gene encoding morphine modulating peptides related to NPFF and FMRFamide". FEBS Lett 409 (3): 426–30. doi:10.1016/S0014-5793(97)00557-7. PMID 9224703. 
2. ^ ^{a b} "Entrez Gene: NPFF neuropeptide FF-amide peptide precursor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8620. 

Further reading

• Panula P, Aarnisalo AA, Wasowicz K (1996). "Neuropeptide FF, a mammalian neuropeptide with multiple functions.". Prog. Neurobiol. 48 (4–5): 461–87. doi:10.1016/0301-0082(96)00001-9. PMID 8804117. 
• Sundblom DM, Panula P, Fyhrquist F (1995). "Neuropeptide FF-like immunoreactivity in human plasma". Peptides 16 (2): 347–50. doi:10.1016/0196-9781(94)00163-4. PMID 7784266. 
• Sundblom DM, Hyrkkö A, Fyhrquist F (1998). "Pulsatile secretion of neuropeptide FF into human blood". Peptides 19 (7): 1165–70. doi:10.1016/S0196-9781(98)00060-6. PMID 9786165. 
• Elshourbagy NA, Ames RS, Fitzgerald LR et al. (2000). "Receptor for the pain modulatory neuropeptides FF and AF is an orphan G protein-coupled receptor". J. Biol. Chem. 275 (34): 25965–71. doi:10.1074/jbc.M004515200. PMID 10851242. 
• Bonini JA, Jones KA, Adham N et al. (2001). "Identification and characterization of two G protein-coupled receptors for neuropeptide FF". J. Biol. Chem. 275 (50): 39324–31. doi:10.1074/jbc.M004385200. PMID 11024015. 
• Mollereau C, Gouardères C, Dumont Y et al. (2001). "Agonist and antagonist activities on human NPFF(2) receptors of the NPY ligands GR231118 and BIBP3226". Br. J. Pharmacol. 133 (1): 1–4. doi:10.1038/sj.bjp.0704049. PMC 1572765. PMID 11325787. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1572765. 
• Catarsi S, Babinski K, Séguéla P (2001). "Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF". Neuropharmacology 41 (5): 592–600. doi:10.1016/S0028-3908(01)00107-1. PMID 11587714. 
• Lefrere I, De Coppet P, Camelin JC et al. (2002). "Neuropeptide AF and FF modulation of adipocyte metabolism. Primary insights from functional genomics and effects on beta-adrenergic responsiveness". J. Biol. Chem. 277 (42): 39169–78. doi:10.1074/jbc.M205084200. PMID 12149260. 
• Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Laemmle B, Schindler M, Beilmann M et al. (2003). "Characterization of the NPGP receptor and identification of a novel short mRNA isoform in human hypothalamus". Regul. Pept. 111 (1–3): 21–9. doi:10.1016/S0167-0115(02)00220-3. PMID 12609745. 
• Ankö ML, Panula P (2006). "Regulation of endogenous human NPFF2 receptor by neuropeptide FF in SK-N-MC neuroblastoma cell line". J. Neurochem. 96 (2): 573–84. doi:10.1111/j.1471-4159.2005.03581.x. PMID 16336216. 
• Roumy M, Lorenzo C, Mazères S et al. (2007). "Physical association between neuropeptide FF and micro-opioid receptors as a possible molecular basis for anti-opioid activity". J. Biol. Chem. 282 (11): 8332–42. doi:10.1074/jbc.M606946200. PMID 17224450.