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Neuropeptide FF (NPFF, FLFQPQRFa) is a mammalian amidated
neuropeptide Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...
originally isolated from bovine brain and characterized as a
pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
-modulating peptide, with anti-opioid activity on morphine-induced analgesia. In humans, neuropeptide FF peptides are encoded by the ''NPFF''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. 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 receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...
s, namely NPFF1 and NPFF2 subtypes and are involved in several physiological functions such as cardiovascular regulation, hormonal control, macrophage activation, body temperature
homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...
and pain modulation. Processing of the NPFFA precursor at basic proteolytic sites should generate a NPFF-containing peptide with three additional
N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...
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 Gonadotropin-inhibitory hormone (GnIH) is a RFamide-related peptide coded by the '' NPVF'' gene in mammals. Discovery GnIH was discovered in 2000. It is an RFamide peptide that significantly reduced luteinizing hormone release in Coturnix Japon ...
), 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 Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...
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 opioid Opioid peptides or opiate peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these p ...
s are necessary for the analgesic properties of spinally injected NPFF while endogenous NPFF peptides are involved in the process of analgesic tolerance/
hyperalgesia Hyperalgesia ( or ; ''hyper'' from Greek ὑπέρ (''huper'') 'over' + ''-algesia'' from Greek ἄλγος (algos) 'pain') is an abnormally increased sensitivity to pain, which may be caused by damage to nociceptors or peripheral nerves and ...
induced by chronic opioid treatment. NPFF also controls the number and metabolic effects of
adipose tissue macrophages Adipose tissue macrophages (ATMs) comprise resident macrophages present in adipose tissue. Besides adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells that includes pre-adipocytes, fibroblasts, vascular endothelial ce ...
, and NPFF is necessary for adipose tissue health.


See also

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Neuropeptide VF precursor Neuropeptide VF precursor, also known as pro-FMRFamide-related neuropeptide VF or RFamide-related peptide precursor, is a propeptide that in mammals is encoded by the ''NPVF'' (or ''RPFP'') gene. The ''NPVF'' gene, and thus the propeptide, are exp ...


References


Further reading

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