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Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neoendorphin. Depolarization of a neuron containing prodynorphin stimulates PC2 processing, which occurs within synaptic vesicles in the presynaptic terminal. Occasionally, prodynorphin is not fully processed, leading to the release of “big dynorphin.” “Big Dynorphin” is a 32-amino acid molecule consisting of both dynorphin A and dynorphin B.
Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. It is secreted alongside other neurotransmitters such as GABA and glutamate.
An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin have been found, one containing leucine ("leu"), and the other containing methionine ("met"). Both are products of the proenkephalin gene.
β-Endorphin (beta-endorphin) is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. It is one of three endorphins that are produced in humans, the others of which include α-endorphin and γ-endorphin.
Nociceptin/orphanin FQ (N/OFQ), a 17-amino acid neuropeptide, is the endogenous ligand for the nociceptin receptor. Nociceptin acts as a potent anti-analgesic, effectively counteracting the effect of pain-relievers; its activation is associated with brain functions such as pain sensation and fear learning.
Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 (intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produced by thyroid C cells whilst CGRP is secreted and stored in the nervous system. This peptide, in humans, exists in two forms: CGRP alpha, and CGRP beta. α-CGRP is a 37-amino acid neuropeptide and is formed by alternative splicing of the calcitonin/CGRP gene located on chromosome 11. β-CGRP is less studied. In humans, β-CGRP differs from α-CGRP by three amino acids and is encoded in a separate, nearby gene. The CGRP family includes calcitonin (CT), adrenomedullin (AM), and amylin (AMY).
Neuropeptide Y receptors are a family of receptors belonging to class A G-protein coupled receptors and they are activated by the closely related peptide hormones neuropeptide Y, peptide YY and pancreatic polypeptide. These receptors are involved in the control of a diverse set of behavioral processes including appetite, circadian rhythm, and anxiety.
Signaling peptide receptor is a type of receptor which binds one or more signaling peptides or signaling proteins.
The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(mu)-opioid peptide (MOP) receptors. The prototypical μ-opioid receptor agonist is morphine, the primary psychoactive alkaloid in opium and for which the receptor was named, with mu being the first letter of Morpheus, the compound's namesake in the original Greek. It is an inhibitory G-protein coupled receptor that activates the Gi alpha subunit, inhibiting adenylate cyclase activity, lowering cAMP levels.
The nociceptin opioid peptide receptor (NOP), also known as the nociceptin/orphanin FQ (N/OFQ) receptor or kappa-type 3 opioid receptor, is a protein that in humans is encoded by the OPRL1 gene. The nociceptin receptor is a member of the opioid subfamily of G protein-coupled receptors whose natural ligand is the 17 amino acid neuropeptide known as nociceptin (N/OFQ). This receptor is involved in the regulation of numerous brain activities, particularly instinctive and emotional behaviors. Antagonists targeting NOP are under investigation for their role as treatments for depression and Parkinson's disease, whereas NOP agonists have been shown to act as powerful, non-addictive painkillers in non-human primates.
The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous ligands. The regions of the brain where the δ-opioid receptor is largely expressed vary from species model to species model. In humans, the δ-opioid receptor is most heavily expressed in the basal ganglia and neocortical regions of the brain.
The tachykinin receptor 1 (TACR1) also known as neurokinin 1 receptor (NK1R) or substance P receptor (SPR) is a G protein coupled receptor found in the central nervous system and peripheral nervous system. The endogenous ligand for this receptor is Substance P, although it has some affinity for other tachykinins. The protein is the product of the TACR1 gene.
GPCR neuropeptide receptors are G-protein coupled receptors which bind various neuropeptides. Members include:
Neuropeptides B/W receptor 1, also known as NPBW1 and GPR7, is a human protein encoded by the NPBWR1 gene. As implied by its name, it and related gene NPBW2 are transmembranes protein that bind Neuropeptide B (NPB) and Neuropeptide W (NPW), both proteins expressed strongly in parts of the brain that regulate stress and fear including the extended amygdala and stria terminalis. When originally discovered in 1995, these receptors had no known ligands and were called GPR7 and GPR8, but at least three groups in the early 2000s independently identified their endogenous ligands, triggering the name change in 2005.
Neuropeptide FF receptor 2, also known as NPFF2 is a human protein encoded by the NPFFR2 gene.
Neuropeptide FF receptor 1, also known as NPFF1 is a human protein, encoded by the NPFFR1 gene.
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.
BIBP-3226 is a drug used in scientific research which acts as a potent and selective antagonist for both the Neuropeptide Y receptor Y1 and also the neuropeptide FF receptor. It was the first non-peptide antagonist developed for the Y1 receptor and has been widely used to help determine its functions in the body. Activation of Y1 is thought to be involved in functions such as regulation of appetite and anxiety, and BIBP-3226 has anxiogenic and anorectic effects, as well as blocking the Y1-mediated corticotropin releasing hormone release. It has also been used as a lead compound to develop a number of newer more potent Y1 antagonists.
Neuropeptide S (NPS) is a neuropeptide found in human and mammalian brain, mainly produced by neurons in the amygdala and between Barrington's nucleus and the locus coeruleus, although NPS-responsive neurons extend projections into many other brain areas. NPS binds specifically to a G protein-coupled receptor, NPSR. Animal studies show that NPS suppresses anxiety and appetite, induces wakefulness and hyperactivity, including hyper-sexuality, and plays a significant role in the extinction of conditioned fear. It has also been shown to significantly enhance dopamine activity in the mesolimbic pathway, and inhibits motility and increases permeability in neurocrine fashion acting through NO in the myenteric plexus in rats and humans.
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 expressed in neurons in the mediobasal hypothalamus. The propeptide is cleaved to form three other peptides, which are:
References
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- ↑ 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 (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.
- ↑ Yang HY, Iadarola MJ (May 2006). "Modulatory roles of the NPFF system in pain mechanisms at the spinal level". Peptides. 27 (5): 943–52. doi:10.1016/j.peptides.2005.06.030. PMID 16443306. S2CID 2197210.
- ↑ 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.
- ↑ Yang HY, Tao T, Iadarola MJ (February 2008). "Modulatory role of neuropeptide FF system in nociception and opiate analgesia". Neuropeptides. 42 (1): 1–18. doi:10.1016/j.npep.2007.06.004. PMID 17854890. S2CID 20901853.
- ↑ Betourne A, Familiades J, Lacassagne L, Halley H, Cazales M, Ducommun B, Lassalle JM, Zajac JM, Frances B (November 2008). "Decreased motivational properties of morphine in mouse models of cancerous- or inflammatory-chronic pain: implication of supraspinal neuropeptide FF(2) receptors" (PDF). Neuroscience. 157 (1): 12–21. doi:10.1016/j.neuroscience.2008.08.045. PMID 18804517. S2CID 31899256.
- ↑ Cline MA, Mathews DS (2008). "Anoretic effects of neuropeptide FF are mediated via central mu and kappa subtypes of opioid receptors and receptor ligands". General and Comparative Endocrinology. 159 (2–3): 125–9. doi:10.1016/j.ygcen.2008.09.001. PMID 18823989.
- ↑ Mollereau C, Mazarguil H, Marcus D, Quelven I, Kotani M, Lannoy V, Dumont Y, Quirion R, Detheux M, Parmentier M, Zajac JM (2002). "Pharmacological characterization of human NPFF(1) and NPFF(2) receptors expressed in CHO cells by using NPY Y(1) receptor antagonists". Eur. J. Pharmacol. 451 (3): 245–56. doi:10.1016/S0014-2999(02)02224-0. PMID 12242085.
- ↑ Fang Q, Guo J, He F, Peng YL, Chang M, Wang R (September 2006). "In vivo inhibition of neuropeptide FF agonism by BIBP3226, an NPY Y1 receptor antagonist". Peptides. 27 (9): 2207–13. doi:10.1016/j.peptides.2006.04.002. PMID 16762456. S2CID 34414256.
- ↑ Fang Q, Wang YQ, He F, Guo J, Guo J, Chen Q, Wang R (April 2008). "Inhibition of neuropeptide FF (NPFF)-induced hypothermia and anti-morphine analgesia by RF9, a new selective NPFF receptors antagonist". Regulatory Peptides. 147 (1–3): 45–51. doi:10.1016/j.regpep.2007.12.007. PMID 18276024. S2CID 37436256.
- ↑ Wang YQ, Guo J, Wang SB, Fang Q, He F, Wang R (July 2008). "Neuropeptide FF receptors antagonist, RF9, attenuates opioid-evoked hypothermia in mice". Peptides. 29 (7): 1183–90. doi:10.1016/j.peptides.2008.02.016. PMID 18406009. S2CID 10797657.
