WordNet
- a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
PrepTutorEJDIC
- =sense organ / 受信装置
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/19 12:51:55」(JST)
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Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors.
There are five known members of the melanocortin receptor system[1] each with differing specificities for melanocortins:[2][3][4]
- MC1R. MC1R is associated with pigmentation genetics.
- MC2R. MC2R is also known as the ACTH receptor or corticotropin receptor because it is specific for ACTH alone.
- MC3R. MC3R
- MC4R. Defects in MC4R are a cause of autosomal dominant obesity, accounting for 6% of all cases of early-onset obesity.[5]
- MC5R. MC5R
These receptors are inhibited by endogenous inverse agonists agouti signalling peptide and agouti-related peptide,[6] and activated by synthetic (i.e. afamelanotide) and endogenous agonist melanocyte-stimulating hormones.[7]
Contents
- 1 Selective ligands
- 1.1 Agonists
- 1.2 Antagonists and inverse agonists
- 2 References
- 3 External links
Selective ligands[edit]
Several selective ligands for the melanocortin receptors are known,[8][9][10][11] and some synthetic compounds have been investigated as potential tanning, anti-obesity and aphrodisiac drugs, with tanning effects mainly from stimulation of MC1,[12] while anorectic and aphrodisiac effects appear to involve both MC3 and MC4.[13] MC1, MC3 and MC4 are widely expressed in the brain, and are also thought to be responsible for effects on mood and cognition.[14][15][16][17]
Agonists[edit]
- Non-selective
- Afamelanotide
- alpha-MSH
- Bremelanotide
- Melanotan II
- MC2 selective
- ACTH
- Cosyntropin
- Tetracosactide
- MC3 selective
- MC4 selective
- beta-MSH
- THIQ
- PF-00446687
Antagonists and inverse agonists[edit]
- MC1 selective
- Agouti signalling peptide
- MC4 selective
- Agouti-related peptide (inverse agonist at both MC3 and MC4)
- HS-014
- HS-024
- MCL-0042[18]
- MCL-0129[19]
- MPB-10
- SHU-9119 (agonist at MC1 and MC5, antagonist at MC3 and MC4)
References[edit]
- ^ Melanocortins and the Melanocortin Receptor
- ^ Voisey J, Carroll L, van Daal A (October 2003). "Melanocortins and their receptors and antagonists". Current Drug Targets 4 (7): 586–97. doi:10.2174/1389450033490858. PMID 14535656.
- ^ Hadley ME, Dorr RT (April 2006). "Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization". Peptides 27 (4): 921–30. doi:10.1016/j.peptides.2005.01.029. PMID 16412534.
- ^ Dores RM (April 2009). "Adrenocorticotropic hormone, melanocyte-stimulating hormone, and the melanocortin receptors: revisiting the work of Robert Schwyzer: a thirty-year retrospective". Annals of the New York Academy of Sciences 1163 (1): 93–100. doi:10.1111/j.1749-6632.2009.04434.x. PMID 19456331.
- ^ Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S (2003). "Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene". N. Engl. J. Med. 348 (12): 1085–95. doi:10.1056/NEJMoa022050. PMID 12646665.
- ^ Chai B, Pogozheva I, Lai Y, Li J, Neubig R, Mosberg H, Gantz I (2005). "Receptor-antagonist interactions in the complexes of agouti and agouti-related protein with human melanocortin 1 and 4 receptors". Biochemistry 44 (9): 3418–31. doi:10.1021/bi0478704. PMID 15736952.
- ^ Pogozheva I, Chai B, Lomize A, Fong T, Weinberg D, Nargund R, Mulholland M, Gantz I, Mosberg H (2005). "Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists". Biochemistry 44 (34): 11329–41. doi:10.1021/bi0501840. PMC 2532597. PMID 16114870.
- ^ Balse-Srinivasan P, Grieco P, Cai M, Trivedi D, Hruby VJ (November 2003). "Structure-activity relationships of gamma-MSH analogues at the human melanocortin MC3, MC4, and MC5 receptors. Discovery of highly selective hMC3R, hMC4R, and hMC5R analogues". Journal of Medicinal Chemistry 46 (23): 4965–73. doi:10.1021/jm030119t. PMID 14584947.
- ^ Wilson KR, Todorovic A, Proneth B, Haskell-Luevano C (2006). "Overview of endogenous and synthetic melanocortin peptides". Cellular and Molecular Biology (Noisy-le-Grand, France) 52 (2): 3–20. PMID 16914082.
- ^ Hruby VJ, Cai M, Cain JP, Mayorov AV, Dedek MM, Trivedi D (2007). "Design, synthesis and biological evaluation of ligands selective for the melanocortin-3 receptor". Current Topics in Medicinal Chemistry 7 (11): 1107–19. doi:10.2174/156802607780906645. PMC 2274922. PMID 17584128.
- ^ Mayorov AV, Cai M, Palmer ES, Dedek MM, Cain JP, Van Scoy AR, Tan B, Vagner J, Trivedi D, Hruby VJ (January 2008). "Structure-activity relationships of cyclic lactam analogues of alpha-melanocyte-stimulating hormone (alpha-MSH) targeting the human melanocortin-3 receptor". Journal of Medicinal Chemistry 51 (2): 187–95. doi:10.1021/jm070461w. PMC 2587288. PMID 18088090.
- ^ Kadekaro AL, Kanto H, Kavanagh R, Abdel-Malek ZA (June 2003). "Significance of the melanocortin 1 receptor in regulating human melanocyte pigmentation, proliferation, and survival". Annals of the New York Academy of Sciences 994 (1): 359–65. doi:10.1111/j.1749-6632.2003.tb03200.x. PMID 12851336.
- ^ King SH, Mayorov AV, Balse-Srinivasan P, Hruby VJ, Vanderah TW, Wessells H (2007). "Melanocortin receptors, melanotropic peptides and penile erection". Current Topics in Medicinal Chemistry 7 (11): 1098–1106. PMC 2694735. PMID 17584130.
- ^ Cragnolini AB, Schiöth HB, Scimonelli TN (June 2006). "Anxiety-like behavior induced by IL-1beta is modulated by alpha-MSH through central melanocortin-4 receptors". Peptides 27 (6): 1451–6. doi:10.1016/j.peptides.2005.10.020. PMID 16325304.
- ^ Catania A (July 2008). "Neuroprotective actions of melanocortins: a therapeutic opportunity". Trends in Neurosciences 31 (7): 353–60. doi:10.1016/j.tins.2008.04.002. PMID 18550183.
- ^ Lasaga M, Debeljuk L, Durand D, Scimonelli TN, Caruso C (October 2008). "Role of alpha-melanocyte stimulating hormone and melanocortin 4 receptor in brain inflammation". Peptides 29 (10): 1825–35. doi:10.1016/j.peptides.2008.06.009. PMID 18625277.
- ^ Gonzalez PV, Schiöth HB, Lasaga M, Scimonelli TN (March 2009). "Memory impairment induced by IL-1beta is reversed by alpha-MSH through central melanocortin-4 receptors". Brain, Behavior, and Immunity 23 (6): 817–22. doi:10.1016/j.bbi.2009.03.001. PMID 19275930.
- ^ Chaki S, Oshida Y, Ogawa S, Funakoshi T, Shimazaki T, Okubo T, Nakazato A, Okuyama S (December 2005). "MCL0042: a nonpeptidic MC4 receptor antagonist and serotonin reuptake inhibitor with anxiolytic- and antidepressant-like activity". Pharmacology, Biochemistry, and Behavior 82 (4): 621–6. doi:10.1016/j.pbb.2005.11.001. PMID 16337261.
- ^ Chaki S, Hirota S, Funakoshi T, Suzuki Y, Suetake S, Okubo T, Ishii T, Nakazato A, Okuyama S (February 2003). "Anxiolytic-like and antidepressant-like activities of MCL0129 (1-[(S)-2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2-methoxynaphthalen-1-yl)butyl]piperazine), a novel and potent nonpeptide antagonist of the melanocortin-4 receptor". The Journal of Pharmacology and Experimental Therapeutics 304 (2): 818–26. doi:10.1124/jpet.102.044826. PMID 12538838.
External links[edit]
- "Melanocortin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- Melanocortin Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
- Calculated spatial position of melanocortin-4 receptor in the lipid bilayer, inactive state with antagonist and active state with agonist
|
Cell surface receptor: G protein-coupled receptors
|
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Class A:
Rhodopsin like |
|
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| Class B: Secretin like |
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Orphan
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- GPR (56
- 64
- 97
- 98
- 110
- 111
- 112
- 113
- 114
- 115
- 116
- 123
- 124
- 125
- 126
- 128
- 133
- 143
- 144
- 155
- 157)
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Other
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- Brain-specific angiogenesis inhibitor (1
- 2
- 3)
- Cadherin (1
- 2
- 3)
- Calcitonin
- CALCRL
- CD97
- Corticotropin-releasing hormone (1
- 2)
- EMR (1
- 2
- 3)
- Glucagon (GR
- GIPR
- GLP1R
- GLP2R)
- Growth hormone releasing hormone
- PACAPR1
- GPR
- Latrophilin (1
- 2
- 3
- ELTD1)
- Methuselah-like proteins
- Parathyroid hormone (1
- 2)
- Secretin
- Vasoactive intestinal peptide (1
- 2)
|
|
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Class C: Metabotropic
glutamate / pheromone |
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Taste
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- TAS1R (1
- 2
- 3)
- 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)
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|
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Other
|
- Calcium-sensing receptor
- GABA B (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)
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|
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Smoothened
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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Neuropeptidergics
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| Cholecystokinin |
|
CCKA
|
- Agonists: Cholecystokinin
- CCK-4
Antagonists: Asperlicin
- Proglumide
- Lorglumide
- Devazepide
- Dexloxiglumide
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|
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CCKB
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- Agonists: Cholecystokinin
- CCK-4
- Gastrin
Antagonists: Proglumide
- CI-988
|
|
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| CRH |
|
CRF1
|
- Agonists: Corticotropin releasing hormone
Antagonists: Antalarmin
- CP-154,526
- Pexacerfont
|
|
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CRF2
|
- Agonists: Corticotropin releasing hormone
|
|
|
| Galanin |
|
GAL1
|
- Agonists: Galanin
- Galanin-like peptide
- Galmic
- Galnon
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|
|
GAL2
|
- Agonists: Galanin
- Galanin-like peptide
- Galmic
- Galnon
|
|
|
GAL3
|
- Agonists: Galanin
- Galmic
- Galnon
|
|
|
| Ghrelin |
- Agonists: Ghrelin
- Capromorelin
- MK-677
- Sermorelin
- SM-130,686
- Tabimorelin
|
|
| GnRH |
- Agonists: Buserelin
- Deslorelin
- GnRH
- Goserelin
- Histrelin
- Leuprorelin
- Nafarelin
- Triptorelin
Antagonists: Abarelix
- Cetrorelix
- Degarelix
- Ganirelix
|
|
| MCH |
|
MCH1
|
- Agonists: Melanin concentrating hormone
Antagonists: ATC-0175
- GW-803,430
- NGD-4715
- SNAP-7941
- SNAP-94847
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|
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MCH2
|
- Agonists: Melanin concentrating hormone
|
|
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| Melanocortin |
|
MC1
|
- Agonists: alpha-MSH
- Afamelanotide
- BMS-470,539
- Bremelanotide
- Melanotan II
Antagonists: Agouti signalling peptide
|
|
|
MC2
|
- Agonists: ACTH
- Cosyntropin
- Tetracosactide
|
|
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MC3
|
- Agonists: alpha-MSH
- Bremelanotide
- Melanotan II
|
|
|
MC4
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- Agonists: alpha-MSH
- Bremelanotide
- Melanotan II
- PF-00446687
- THIQ
Antagonists: Agouti-related peptide
|
|
|
MC5
|
- Agonists: alpha-MSH
- Melanotan II
|
|
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| Neuropeptide S |
- Agonists: Neuropeptide S
Antagonists: SHA-68
|
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| Neuropeptide Y |
|
Y1
|
- Agonists: Neuropeptide Y
- Peptide YY
Antagonists: BIBP-3226
|
|
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Y2
|
- Agonists: Neuropeptide Y
- Peptide YY
Antagonists: BIIE-0246
|
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Y4
|
- Agonists: Neuropeptide Y
- Pancreatic polypeptide
- Peptide YY
Antagonists: UR-AK49
|
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Y5
|
- Agonists: Neuropeptide Y
- Peptide YY
Antagonists: Lu AA-33810
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|
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| Neurotensin |
|
NTS1
|
- Agonists: Neurotensin
- Neuromedin N
Antagonists: SR-48692
- SR-142,948
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NTS2
|
- Agonists: Neurotensin
Antagonists: Levocabastine
- SR-142,948
|
|
|
| Orexin |
|
OX1
|
- Agonists: Orexin-A
Antagonists: Almorexant
- SB-334,867
- SB-408,124
- SB-649,868
- Suvorexant
|
|
|
OX2
|
- Agonists: Orexin-A
Antagonists: Almorexant
- SB-649,868
- Suvorexant
- TCS-OX2-29
|
|
|
| Oxytocin |
- Agonists: Carbetocin
- Demoxytocin
- Oxytocin
- WAY-267,464
Antagonists: Atosiban
- Epelsiban
- L-371,257
- L-368,899
- Retosiban
|
|
| Tachykinin |
|
NK1
|
- Agonists: Substance P
Antagonists: Aprepitant
- Befetupitant
- Casopitant
- CI-1021
- CP-96,345
- CP-99,994
- CP-122,721
- Dapitant
- Ezlopitant
- FK-888
- Fosaprepitant
- GR-203,040
- GW-597,599
- HSP-117
- L-733,060
- L-741,671
- L-743,310
- L-758,298
- Lanepitant
- LY-306,740
- Maropitant
- Netupitant
- NKP-608
- Nolpitantium
- Orvepitant
- RP-67,580
- SDZ NKT 343
- Vestipitant
- Vofopitant
|
|
|
NK2
|
- Agonists: Neurokinin A
Antagonists: GR-159,897
- Ibodutant
- Saredutant
|
|
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NK3
|
- Agonists: Neurokinin B
Antagonists: Osanetant
- Talnetant
|
|
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| Vasopressin |
|
V1A
|
- Agonists: Desmopressin
- Felypressin
- Ornipressin
- Terlipressin
- Vasopressin
Antagonists: Conivaptan
- Demeclocycline
- Relcovaptan
|
|
|
V1B
|
- Agonists: Felypressin
- Ornipressin
- Terlipressin
- Vasopressin
Antagonists: Demeclocycline
- Nelivaptan
|
|
|
V2
|
- Agonists: Desmopressin
- Ornipressin
- Vasopressin
Antagonists: Conivaptan
- Demeclocycline
- Lixivaptan
- Mozavaptan
- Satavaptan
- Tolvaptan
|
|
|
UpToDate Contents
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English Journal
- Modeling the interactions between MC2R and ACTH models from human.
- Dieudonné M1, Ramesh KV.
- Journal of biomolecular structure & dynamics.J Biomol Struct Dyn.2015 Apr;33(4):770-88. doi: 10.1080/07391102.2014.910475. Epub 2014 Apr 28.
- Melanocortin system is composed of four peptide hormones namely α-, β-, -γ, and adrenocorticotropic hormone (ACTH), derived from post-translational cleavage of a polypeptide precursor 'proopiomelanocortin (POMC).' Among these hormones, ACTH, a 38 amino acid residue peptide fragment is an importan
- PMID 24708442
- Alpha-melanocyte stimulating hormone modulates ethanol self-administration in posterior ventral tegmental area through melanocortin-4 receptors.
- Shelkar GP1, Kale AD, Singh U, Singru PS, Subhedar NK, Kokare DM.
- Addiction biology.Addict Biol.2015 Mar;20(2):302-15. doi: 10.1111/adb.12126. Epub 2014 Mar 18.
- Although the role of alpha-melanocyte stimulating hormone (α-MSH) in alcohol seeking behaviour in rats has been demonstrated, the underlying mechanisms are not understood. Herein, we test the hypothesis that α-MSH might have a permissive effect in promoting the reward action of ethanol. Rats were
- PMID 24635847
- A critical role for the melanocortin 4 receptor in stress-induced relapse to nicotine seeking in rats.
- Qi X1, Yamada H, Corrie LW, Ji Y, Bauzo RM, Alexander JC, Bruijnzeel AW.
- Addiction biology.Addict Biol.2015 Mar;20(2):324-35. doi: 10.1111/adb.12129. Epub 2014 Feb 24.
- Tobacco addiction is characterized by a lack of control over smoking and relapse after periods of abstinence. Smoking cessation leads to a dysphoric state that contributes to relapse to smoking. After the acute withdrawal phase, exposure to stressors increases the risk for relapse. Blockade of melan
- PMID 24612112
Japanese Journal
- Biochemistry: Mutations in the melanocortin 1 receptor, β-defensin103 and agouti signaling protein genes, and their association with coat color phenotypes in Alita-inu doges
- Oguro-Okano Mieko,Honda Mioko,Yamazaki Kaoru [他]
- 日本獣醫學会会誌 73(7), 853-858, 2011-07
- NAID 40018935651
- Obesity-Related Mechanism of Food Intake Suppression
- He Junfeng,Wong Siew Sun,Qu Yating,Xie Menzhou
- Journal of brain science 36, 61-80, 2011-03-30
- … In this article, leptin, insulin, melanocortin receptor, dopamine, serotonin, norepinephrine, brain-derived neurotrophic factor, cannabinoid-1 receptor blocker, cytokines, tumor necrosis factor-alpha, lipopolysaccharide, interleukin, cholecystokinin, enterostatin, estrogen, testosterone and apolipoprotein E will be discussed. …
- NAID 110008574016
Related Links
- The official name of this gene is “melanocortin 4 receptor.” MC4R is the gene's official symbol. The MC4R gene is also known by other names, listed below. Read more about gene names and symbols on the About page.
- The protein encoded by this gene is a membrane-bound receptor and member of the melanocortin receptor family. The encoded protein interacts with adrenocorticotropic and MSH hormones and is mediated by G ...
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- 関
- メラノコルチン受容体
[★]
1型メラノコルチン受容体
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2型メラノコルチン受容体
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3型メラノコルチン受容体