Neuropeptide FF receptor

InterPro Family

neuropeptide FF receptor 1

Identifiers
Symbol| NPFFR1
Alt. symbols| GPR147
NCBI gene| 64106
HGNC| 17425
OMIM| 607448
RefSeq| NM_022146
UniProt| Q9GZQ6
Other data
Locus| Chr. 10 q21-q22
| Search for

Structures| Swiss-model
Domains| InterPro
neuropeptide FF receptor 2

Identifiers
Symbol| NPFFR2
Alt. symbols| GPR74
NCBI gene| 10886
HGNC| 4525
OMIM| 607449
RefSeq| NM_004885
UniProt| Q9Y5X5
Other data
Locus| Chr. 4 q21
| Search for

Structures| Swiss-model
Domains| InterPro

The neuropeptide FF receptors[1] are members of the G-protein coupled receptor superfamily of integral membrane proteins which bind the pain modulatory neuropeptides AF and FF.[2] The Neuropeptide FF receptor family is a member of the G protein-coupled receptor superfamily containing two subtypes, NPFF1 and NPFF2, which exhibit a high affinity for Neuropeptide FF (NPFF) peptides. NPFF1 is broadly distributed in the central nervous system with the highest levels found in the limbic system and the hypothalamus. NPFF2 is present in high density, particularly in mammals in the superficial layers of the spinal cord where it is involved in nociception and modulation of opioid functions. These receptors participate to the modulation of opioid receptor function in the brain and spinal cord, and can either reduce or increase opioid receptor function depending which tissue they are released in, reflecting a complex role for neuropeptide FF in pain responses. [3][4][5][6][7]

NPFF receptors are coupled to G proteins and regulate adenylyl cyclase in recombinant cell lines (CHO, HEK 293, SH-SY5Y). NPFF receptors are also coupled to voltage-gated N-type Ca2+ channels.

## Ligands

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### Agonists

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* Neuropeptide AF
* Neuropeptide FF
* Neuropeptide SF (RFRP-1)
* Neuropeptide VF (RFRP-3)

### Antagonists

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* BIBP-3226 (mixed NPFF1 / NPY1 antagonist)[8][9]
* RF-9[10][11]

## References

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1. ^ Parker RM, Copeland NG, Eyre HJ, Liu M, Gilbert DJ, Crawford J, Couzens M, Sutherland GR, Jenkins NA, Herzog H (2000). "Molecular cloning and characterisation of GPR74 a novel G-protein coupled receptor closest related to the Y-receptor family". Brain Res. Mol. Brain Res. 77 (2): 199–208. doi:10.1016/S0169-328X(00)00052-8. PMID 10837915.
2. ^ 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.
3. ^ 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.
4. ^ 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.
5. ^ 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.
6. ^ 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.
7. ^ 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.
8. ^ 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.
9. ^ 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.
10. ^ 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.
11. ^ 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.

## External links

[edit]

* "Neuropeptide FF Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2007-11-03.
* neuropeptide+FF+receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

* v
* t
* e

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin-like

| Neurotransmitter|

| Adrenergic|

* α1 (A
* B
* D)
* α2 (A
* B
* C)
* β1
* β2
* β3

|

Purinergic|

* Adenosine (A1
* A2A
* A2B
* A3)
* P2Y (1
* 2
* 4
* 5
* 6
* 8
* 9
* 10
* 11
* 12
* 13
* 14)

Serotonin|

* (all but 5-HT3) 5-HT1 (A
* B
* D
* E
* F)
* 5-HT2 (A
* B
* C)
* 5-HT (4
* 5A
* 6
* 7)

Other|

* Acetylcholine (M1
* M2
* M3
* M4
* M5)
* Dopamine
* D1
* D2
* D3
* D4
* D5
* GHB receptor
* Histamine
* H1
* H2
* H3
* H4
* Melatonin (1A
* 1B
* 1C)
* TAAR (1
* 2
* 5
* 6
* 8
* 9)

Metabolites and
signaling molecules|

| Eicosanoid|

* CysLT (1
* 2)
* LTB4
* 1
* 2
* FPRL1
* OXE
* Prostaglandin
* DP (1
* 2), EP (1
* 2
* 3
* 4), FP
* Prostacyclin
* Thromboxane

|

Other|

* Bile acid
* Cannabinoid (CB1
* CB2, GPR (18
* 55
* 119))
* EBI2
* Estrogen
* Free fatty acid (1
* 2
* 3
* 4)
* Hydroxycarboxylic acids
* 1
* 2
* 3
* Lysophosphatidic acid (1
* 2
* 3
* 4
* 5
* 6)
* Lysophospholipid (1
* 2
* 3
* 4
* 5
* 6
* 7
* 8)
* Oxoglutarate
* PAF
* Sphingosine-1-phosphate (1
* 2
* 3
* 4
* 5)
* Succinate

Peptide|

| Neuropeptide|

* B/W (1
* 2)
* FF (1
* 2)
* S
* Y (1
* 2
* 4
* 5)
* Neuromedin (B
* U (1
* 2))
* Neurotensin (1
* 2)

|

Other|

* Anaphylatoxin (C3a
* C5a (1
* 2))
* Angiotensin (1
* 2)
* Apelin
* Bombesin
* BRS3
* GRPR
* NMBR)
* Bradykinin (B1
* B2)
* Chemokine
* Cholecystokinin (A
* B)
* Endothelin
* A
* B
* Formyl peptide (1
* 2
* 3)
* FSH
* Galanin (1
* 2
* 3)
* Gonadotropin-releasing hormone (1
* 2)
* Ghrelin
* Kisspeptin
* Luteinizing hormone/choriogonadotropin
* MAS (1
* 1L
* D
* E
* F
* G
* X1
* X2
* X3
* X4)
* Melanocortin (1
* 2
* 3
* 4
* 5)
* MCHR (1
* 2)
* Motilin
* Opioid (Delta
* Kappa
* Mu
* Nociceptin & Zeta, but not Sigma)
* Orexin (1
* 2)
* Oxytocin
* Prokineticin (1
* 2)
* Prolactin-releasing peptide
* Relaxin (1
* 2
* 3
* 4)
* Somatostatin (1
* 2
* 3
* 4
* 5)
* Tachykinin (1
* 2
* 3)
* Thyrotropin
* Thyrotropin-releasing hormone
* Urotensin-II
* Vasopressin (1A
* 1B
* 2)

Miscellaneous|

| Taste, bitter|

* TAS2R
* 1
* 3
* 4
* 5
* 7
* 8
* 9
* 10
* 13
* 14
* 16
* 19
* 20
* 30
* 31
* 38
* 39
* 40
* 41
* 42
* 43
* 45
* 46
* 50
* 60
* Vomeronasal receptor type 1

|

Orphan|

* GPR (1
* 3
* 4
* 6
* 12
* 15
* 17
* 18
* 19
* 20
* 21
* 22
* 23
* 25
* 26
* 27
* 31
* 32
* 33
* 34
* 35
* 37
* 39
* 42
* 44
* 45
* 50
* 52
* 55
* 61
* 62
* 63
* 65
* 68
* 75
* 78
* 81
* 82
* 83
* 84
* 85
* 87
* 88
* 92
* 101
* 103
* 109A
* 109B
* 119
* 120
* 132
* 135
* 137B
* 139
* 141
* 142
* 146
* 148
* 149
* 150
* 151
* 152
* 153
* 160
* 161
* 162
* 171
* 173
* 174
* 176
* 177
* 182
* 183)

Other|

* Adrenomedullin
* Olfactory
* Opsin (3
* 4
* 5
* 1LW
* 1MW
* 1SW
* RGR
* RRH)
* Protease-activated (1
* 2
* 3
* 4)
* SREB (1
* 2
* 3)

Class B: Secretin-like

| Adhesion|

* ADGRB
* Brain-specific angiogenesis inhibitor
* 1
* 2
* 3
* ADGRC
* Cadherin
* 1
* 2
* 3
* ADGRE
* EMR
* 1
* 2
* 3
* CD97
* ADGRG
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* ADGRL
* Latrophilin
* 1
* 2
* 3
* ELTD1

|

Orphan|

* GPR (56
* 64
* 97
* 98
* 110
* 111
* 112
* 113
* 114
* 115
* 116
* 123
* 124
* 125
* 126
* 128
* 133
* 143
* 144
* 155
* 157)

Other|

* Calcitonin
* CALCRL
* Corticotropin-releasing hormone (1
* 2)
* Glucagon (GR
* GIPR
* GLP1R
* GLP2R)
* Growth-hormone-releasing hormone
* PACAPR1
* GPR
* Methuselah-like proteins
* Parathyroid hormone (1
* 2)
* Secretin
* Vasoactive intestinal peptide (1
* 2)

Class C: Metabotropic glutamate / pheromone

| Taste, sweet|

* TAS1R
* 1
* 2
* 3
* Vomeronasal receptor, type 2

|

Other|

* Calcium-sensing receptor
* GABAB (1
* 2)
* Glutamate receptor (Metabotropic glutamate (1
* 2
* 3
* 4
* 5
* 6
* 7
* 8))
* GPRC6A
* GPR (156
* 158
* 179)
* RAIG (1
* 2
* 3
* 4)

Class F: Frizzled & Smoothened

| Frizzled|

* Frizzled (1
* 2
* 3
* 4
* 5
* 6
* 7
* 8
* 9
* 10)

|

Smoothened|

* Smoothened

* v
* t
* e

Neuropeptide receptors

G protein-coupled receptor|

| Hormone receptors|

| Hypothalamic|

* CRH
* FSH
* LHRH
* TRH
* Somatostatin

|

Pituitary|

* Vasopressin
* 1A
* 1B
* 2
* Oxytocin
* LHCG
* TSH

Other|

* Atrial natriuretic factor
* NPR3
* Calcitonin
* Cholecystokinin
* A
* B
* VIP

Opioid receptors|

* Delta
* Kappa
* Mu
* Nociceptin

Other neuropeptide receptors|

* Angiotensin
* Bradykinin
* B1
* B2
* Tachykinin
* TACR1
* Calcitonin gene-related peptide
* Galanin
* GPCR neuropeptide
* B/W
* FF
* S
* Y
* Neurotensin

Type I cytokine receptor|

* GH
* Prolactin

Enzyme-linked receptor|

* Atrial natriuretic factor
* NPR1
* NPR2

Other|

* Sigma
* 1
* 2

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