Neuropeptide FF

Neuropeptide FF (NPFF, 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.

NPFF
Identifiers
Aliases	NPFF, FMRFAL, neuropeptide FF-amide peptide precursor
External IDs	OMIM: 604643; MGI: 1891708; HomoloGene: 48236; GeneCards: NPFF; OMA:NPFF - orthologs
Gene location (Human) Chr. Chromosome 12 (human) Band 12q13.13 Start 53,506,688 bp End 53,507,484 bp
Gene location (Mouse) Chr. Chromosome 15 (mouse) Band 15|15 F3 Start 102,432,274 bp End 102,433,377 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle gonad epithelium of colon granulocyte ganglionic eminence apex of heart olfactory zone of nasal mucosa C1 segment stromal cell of endometrium mucosa of transverse colon Top expressed in bone marrow pancreas islet of Langerhans adrenal gland urinary bladder skeletal muscle tissue morula zone of skin white adipose tissue spleen More reference expression data BioGPS More reference expression data
Gene ontology Molecular function signaling receptor binding G protein-coupled receptor binding neuropeptide hormone activity Cellular component vesicle extracellular region postsynapse extracellular space dendrite perikaryon axon terminus Biological process negative regulation of insulin secretion regulation of sensory perception of pain maternal process involved in female pregnancy positive regulation of cytosolic calcium ion concentration acute inflammatory response to antigenic stimulus negative regulation of appetite vasopressin secretion regulation of membrane depolarization negative regulation of heart rate response to morphine positive regulation of blood pressure spinal cord development neuropeptide signaling pathway somatostatin secretion chemical synaptic transmission excitatory postsynaptic potential regulation of signaling receptor activity G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8620 54615 Ensembl ENSG00000139574 ENSMUSG00000023052 UniProt O15130 Q9WVA8 RefSeq (mRNA) NM_003717 NM_001320296 NM_018787 RefSeq (protein) NP_001307225 NP_003708 NP_061257 Location (UCSC) Chr 12: 53.51 – 53.51 Mb Chr 15: 102.43 – 102.43 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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.

Function

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, macrophage activation, body temperature homeostasis and pain modulation.

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 (RFRPs, 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.

NPFF also controls the number and metabolic effects of adipose tissue macrophages, and NPFF is necessary for adipose tissue health.

See also

• Neuropeptide VF precursor

Further reading

• Panula P, Aarnisalo AA, Wasowicz K (1996). "Neuropeptide FF, a mammalian neuropeptide with multiple functions". Progress in Neurobiology. 48 (4–5): 461–87. doi:10.1016/0301-0082(96)00001-9. PMID 8804117. S2CID 5985620.
• 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. S2CID 27839755.
• 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. S2CID 25714310.
• Elshourbagy NA, Ames RS, Fitzgerald LR, Foley JJ, Chambers JK, Szekeres PG, Evans NA, Schmidt DB, Buckley PT, Dytko GM, Murdock PR, Milligan G, Groarke DA, Tan KB, Shabon U, Nuthulaganti P, Wang DY, Wilson S, Bergsma DJ, Sarau HM (August 2000). "Receptor for the pain modulatory neuropeptides FF and AF is an orphan G protein-coupled receptor". The Journal of Biological Chemistry. 275 (34): 25965–71. doi:10.1074/jbc.M004515200. PMID 10851242.
• Bonini JA, Jones KA, Adham N, Forray C, Artymyshyn R, Durkin MM, Smith KE, Tamm JA, Boteju LW, Lakhlani PP, Raddatz R, Yao WJ, Ogozalek KL, Boyle N, Kouranova EV, Quan Y, Vaysse PJ, Wetzel JM, Branchek TA, Gerald C, Borowsky B (December 2000). "Identification and characterization of two G protein-coupled receptors for neuropeptide FF". The Journal of Biological Chemistry. 275 (50): 39324–31. doi:10.1074/jbc.M004385200. PMID 11024015.
• Mollereau C, Gouardères C, Dumont Y, Kotani M, Detheux M, Doods H, Parmentier M, Quirion R, Zajac JM (May 2001). "Agonist and antagonist activities on human NPFF(2) receptors of the NPY ligands GR231118 and BIBP3226". British Journal of Pharmacology. 133 (1): 1–4. doi:10.1038/sj.bjp.0704049. PMC 1572765. PMID 11325787.
• Catarsi S, Babinski K, Séguéla P (October 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. S2CID 568441.
• Lefrere I, De Coppet P, Camelin JC, Le Lay S, Mercier N, Elshourbagy N, Bril A, Berrebi-Bertrand I, Feve B, Krief S (October 2002). "Neuropeptide AF and FF modulation of adipocyte metabolism. Primary insights from functional genomics and effects on beta-adrenergic responsiveness". The Journal of Biological Chemistry. 277 (42): 39169–78. doi:10.1074/jbc.M205084200. PMID 12149260.
• Laemmle B, Schindler M, Beilmann M, Hamilton BS, Doods HN, Wieland HA (March 2003). "Characterization of the NPGP receptor and identification of a novel short mRNA isoform in human hypothalamus". Regulatory Peptides. 111 (1–3): 21–9. doi:10.1016/S0167-0115(02)00220-3. PMID 12609745. S2CID 24049458.
• Ankö ML, Panula P (January 2006). "Regulation of endogenous human NPFF2 receptor by neuropeptide FF in SK-N-MC neuroblastoma cell line". Journal of Neurochemistry. 96 (2): 573–84. doi:10.1111/j.1471-4159.2005.03581.x. PMID 16336216. S2CID 26460239.
• Roumy M, Lorenzo C, Mazères S, Bouchet S, Zajac JM, Mollereau C (March 2007). "Physical association between neuropeptide FF and micro-opioid receptors as a possible molecular basis for anti-opioid activity". The Journal of Biological Chemistry. 282 (11): 8332–42. doi:10.1074/jbc.M606946200. PMID 17224450.