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)[1] Band 12q13.13 Start 53,506,688 bp[1] End 53,507,484 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 F3 Start 102,432,274 bp[2] End 102,433,377 bp[2]
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 [3] [4]
Wikidata
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Chemical structure of neuropeptide FF

In humans, neuropeptide FF peptides are encoded by the NPFF gene. Two genes encoding two different receptors (NPFF1 and NPFF2) and two precursors [NPFFA (this gene) and NPFFB (NPVF)] have been cloned in several mammalian species.^[5][6][7][8]

Processing

Processing of the NPFFA precursor at basic proteolytic sites generates 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.

Function

Neuropeptide FF (NPFF) and several other RFamide related peptides issued from two precursors, interact with varying 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.^[6]

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.^[9][10][11]

As well as affecting pain perception, NPFF also modulates related processes such as inflammation and macrophage activation,^[12][13] and neurogenesis during recovery from brain injury,^[14] as well as being linked to mood disorders such as depression and anxiety.^[15] Peripheral NPFF receptors are also involved in the regulation of blood pressure.^[16]

NPFF also controls the number and metabolic effects of adipose tissue macrophages, and NPFF is necessary for adipose tissue health,^[17] but over-activation of NPFFR2 receptors has been linked to obesity and metabolic syndrome.^[18]

See also

• Neuropeptide VF precursor